1<?xml version="1.0" ?><!DOCTYPE PubmedArticleSet PUBLIC "-//NLM//DTD PubMedArticle, 1st January 2019//EN" "https://dtd.nlm.nih.gov/ncbi/pubmed/out/pubmed_190101.dtd"> 2<PubmedArticleSet><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30446446 </PMID><DateCompleted><Year>2020 </Year><Month>07 </Month><Day>23 </Day></DateCompleted><DateRevised><Year>2020 </Year><Month>07 </Month><Day>23 </Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1873-2496 </ISSN><JournalIssue CitedMedium="Internet"><Volume>37 </Volume><Issue>11 </Issue><PubDate><Year>2019 </Year><Month>11 </Month></PubDate></JournalIssue><Title>Urologic oncology </Title><ISOAbbreviation>Urol Oncol </ISOAbbreviation></Journal><ArticleTitle>Molecular footprints of muscle-invasive bladder cancer in smoking and nonsmoking patients. </ArticleTitle><Pagination><MedlinePgn>818-825 </MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1078-1439(18)30381-8 </ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.urolonc.2018.09.017 </ELocationID><Abstract><AbstractText Label="BACKGROUND">Bladder cancer is the fifth most common cancer in the United States and smoking is the largest known risk factor. Tobacco-derived carcinogens may induce the accumulation of somatic mutations in urothelial cells, and likely promote tumorigenesis. However, it is still unknown whether smoking-induced bladder carcinogenesis results in tumors with distinctive molecular features that can be therapeutically exploited. </AbstractText><AbstractText Label="METHODS">We investigated the genomic alterations of human bladder cancer and examined their association with patient smoking history. We performed bioinformatic analyses and looked at differences in gene expression, somatic mutations, and DNA mutational signatures comparing nonsmokers, reformed smokers, and current smokers. </AbstractText><AbstractText Label="RESULTS">We detected a limited set of gene expression and gene mutation differences between smokers and nonsmokers. We also identified a specific mutational signature that is enriched in tumors from smokers. This mutational signature was described before and has been linked to specific DNA repair defects in human bladder tumors, as well as to the direct effect of nitrosamine carcinogens in the BBN murine model of bladder cancer. </AbstractText><AbstractText Label="CONCLUSION">We showed associations between smoking status and selected mutational signatures, which could provide insights in the biology of bladder carcinogenesis and tumor progression. </AbstractText><CopyrightInformation>Published by Elsevier Inc. </CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fantini </LastName><ForeName>Damiano </ForeName><Initials>D </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Seiler </LastName><ForeName>Roland </ForeName><Initials>R </Initials><AffiliationInfo><Affiliation>Department of Urology, University Hospital Bern, Bern, Switzerland. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meeks </LastName><ForeName>Joshua J </ForeName><Initials>JJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; Department of Biochemistry and Molecular Genetics, Northwestern University, Chicago, IL. Electronic address: joshua.meeks@northwestern.edu. </Affiliation></AffiliationInfo></Author></AuthorList><Language>eng </Language><GrantList CompleteYN="Y"><Grant><GrantID>I01 BX003692 </GrantID><Acronym>BX </Acronym><Agency>BLRD VA </Agency><Country>United States </Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article </PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018 </Year><Month>11 </Month><Day>13 </Day></ArticleDate></Article><MedlineJournalInfo><Country>United States </Country><MedlineTA>Urol Oncol </MedlineTA><NlmUniqueID>9805460 </NlmUniqueID><ISSNLinking>1078-1439 </ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D014408">Biomarkers, Tumor </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D002273">Carcinogens </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="C103539">GPR15 protein, human </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D043562">Receptors, G-Protein-Coupled </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D018000">Receptors, Peptide </NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.5.4.5 </RegistryNumber><NameOfSubstance UI="D000071478">APOBEC Deaminases </NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM </CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000071478" MajorTopicYN="N">APOBEC Deaminases </DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis </QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014408" MajorTopicYN="N">Biomarkers, Tumor </DescriptorName><QualifierName UI="Q000032" MajorTopicYN="Y">analysis </QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics </QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D063646" MajorTopicYN="N">Carcinogenesis </DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced </QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002273" MajorTopicYN="N">Carcinogens </DescriptorName><QualifierName UI="Q000633" MajorTopicYN="N">toxicity </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015972" MajorTopicYN="N">Gene Expression Regulation, Neoplastic </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059645" MajorTopicYN="N">Mutation Rate </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000078405" MajorTopicYN="N">Non-Smokers </DescriptorName><QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043562" MajorTopicYN="N">Receptors, G-Protein-Coupled </DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis </QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018000" MajorTopicYN="N">Receptors, Peptide </DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis </QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000074285" MajorTopicYN="N">Smokers </DescriptorName><QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012907" MajorTopicYN="N">Smoking </DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014026" MajorTopicYN="N">Tobacco </DescriptorName><QualifierName UI="Q000633" MajorTopicYN="Y">toxicity </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015854" MajorTopicYN="N">Up-Regulation </DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001743" MajorTopicYN="N">Urinary Bladder </DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects </QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001749" MajorTopicYN="N">Urinary Bladder Neoplasms </DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology </QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality </QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019459" MajorTopicYN="N">Urothelium </DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects </QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology </QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">APOBEC mutagenesis </Keyword><Keyword MajorTopicYN="Y">BBN mouse model </Keyword><Keyword MajorTopicYN="Y">Bladder cancer </Keyword><Keyword MajorTopicYN="Y">Cancer genome </Keyword><Keyword MajorTopicYN="Y">Mutational signatures </Keyword><Keyword MajorTopicYN="Y">Smoking-related carcinogenesis </Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018 </Year><Month>06 </Month><Day>06 </Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018 </Year><Month>08 </Month><Day>24 </Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018 </Year><Month>09 </Month><Day>03 </Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018 </Year><Month>11 </Month><Day>18 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020 </Year><Month>7 </Month><Day>24 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018 </Year><Month>11 </Month><Day>18 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate></History><PublicationStatus>ppublish </PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30446446 </ArticleId><ArticleId IdType="pii">S1078-1439(18)30381-8 </ArticleId><ArticleId IdType="doi">10.1016/j.urolonc.2018.09.017 </ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30421072 </PMID><DateCompleted><Year>2020 </Year><Month>02 </Month><Day>18 </Day></DateCompleted><DateRevised><Year>2020 </Year><Month>02 </Month><Day>25 </Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1433-8726 </ISSN><JournalIssue CitedMedium="Internet"><Volume>37 </Volume><Issue>9 </Issue><PubDate><Year>2019 </Year><Month>Sep </Month></PubDate></JournalIssue><Title>World journal of urology </Title><ISOAbbreviation>World J Urol </ISOAbbreviation></Journal><ArticleTitle>Genomic classification and risk stratification of bladder cancer. </ArticleTitle><Pagination><MedlinePgn>1751-1757 </MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00345-018-2558-2 </ELocationID><Abstract><AbstractText>Bladder cancer is the fourth most common cancer in men and fifth most common overall. The use of next-generation sequencing (NGS) approaches is crucial to precisely characterize the molecular defects of tumors, and this information could be combined with other clinical data, such as tumor histology and TNM staging, with the goal of precise tumor classification. In many settings, targeted NGS is evaluated in patients with first- and second-line metastatic cancer. Yet, in the decade to come we anticipate increased application of precision oncology at all stages of bladder cancer with the aim of customizing cancer treatment. Here, we review the genomic and transcriptomic features associated with risk stratification in bladder cancer and summarize the current efforts for precision oncology in localized urothelial carcinomas. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fantini </LastName><ForeName>Damiano </ForeName><Initials>D </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Cancer Center, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meeks </LastName><ForeName>Joshua J </ForeName><Initials>JJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Chicago, IL, USA. joshua.meeks@northwestern.edu. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, IL, USA. joshua.meeks@northwestern.edu. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Cancer Center, Chicago, IL, USA. joshua.meeks@northwestern.edu. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Jesse Brown VA Medical Center, Chicago, IL, USA. joshua.meeks@northwestern.edu. </Affiliation></AffiliationInfo></Author></AuthorList><Language>eng </Language><GrantList CompleteYN="Y"><Grant><GrantID>I01 BX003692 </GrantID><Acronym>BX </Acronym><Agency>BLRD VA </Agency><Country>United States </Country></Grant><Grant><GrantID>BX003692 </GrantID><Agency>Office of Research and Development </Agency><Country/></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article </PublicationType><PublicationType UI="D016454">Review </PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018 </Year><Month>11 </Month><Day>12 </Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany </Country><MedlineTA>World J Urol </MedlineTA><NlmUniqueID>8307716 </NlmUniqueID><ISSNLinking>0724-4983 </ISSNLinking></MedlineJournalInfo><CitationSubset>IM </CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D023281" MajorTopicYN="Y">Genomics </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009361" MajorTopicYN="N">Neoplasm Invasiveness </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018570" MajorTopicYN="N">Risk Assessment </DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001749" MajorTopicYN="N">Urinary Bladder Neoplasms </DescriptorName><QualifierName UI="Q000145" MajorTopicYN="Y">classification </QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics </QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology </QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Biomarker </Keyword><Keyword MajorTopicYN="N">Bladder cancer </Keyword><Keyword MajorTopicYN="N">Classifier </Keyword><Keyword MajorTopicYN="N">Genetic mutation </Keyword><Keyword MajorTopicYN="N">Risk-classification </Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018 </Year><Month>09 </Month><Day>10 </Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018 </Year><Month>11 </Month><Day>03 </Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018 </Year><Month>11 </Month><Day>14 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020 </Year><Month>2 </Month><Day>19 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018 </Year><Month>11 </Month><Day>14 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate></History><PublicationStatus>ppublish </PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30421072 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Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meeks </LastName><ForeName>Joshua J </ForeName><Initials>JJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine Northwestern University, Chicago, IL 60611, USA. </Affiliation></AffiliationInfo></Author></AuthorList><Language>eng </Language><GrantList CompleteYN="Y"><Grant><GrantID>I01 BX003692 </GrantID><Acronym>BX </Acronym><Agency>BLRD VA </Agency><Country>United States </Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016421">Editorial </PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018 </Year><Month>06 </Month><Day>29 </Day></ArticleDate></Article><MedlineJournalInfo><Country>United States </Country><MedlineTA>Oncoscience </MedlineTA><NlmUniqueID>101636666 </NlmUniqueID><ISSNLinking>2331-4737 </ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">BBN tumors </Keyword><Keyword MajorTopicYN="N">bladder cancer </Keyword><Keyword MajorTopicYN="N">cancer genomics </Keyword><Keyword MajorTopicYN="N">cancer models </Keyword><Keyword MajorTopicYN="N">epigenetic factors </Keyword></KeywordList><CoiStatement>CONFLICTS OF INTEREST The authors declare that they have no competing interests. </CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018 </Year><Month>05 </Month><Day>02 </Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018 </Year><Month>05 </Month><Day>09 </Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018 </Year><Month>7 </Month><Day>24 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018 </Year><Month>7 </Month><Day>24 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018 </Year><Month>7 </Month><Day>24 </Day><Hour>6 </Hour><Minute>1 </Minute></PubMedPubDate></History><PublicationStatus>epublish </PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30035181 </ArticleId><ArticleId IdType="doi">10.18632/oncoscience.439 </ArticleId><ArticleId IdType="pii">439 </ArticleId><ArticleId IdType="pmc">PMC6049309 </ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Int J Cancer. 2015 Mar 1;136(5):E359-86 </Citation><ArticleIdList><ArticleId IdType="pubmed">25220842 </ArticleId></ArticleIdList></Reference><Reference><Citation>Oncogene. 2018 Apr;37(14):1911-1925 </Citation><ArticleIdList><ArticleId IdType="pubmed">29367767 </ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2017 Oct 19;171(3):540-556.e25 </Citation><ArticleIdList><ArticleId IdType="pubmed">28988769 </ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Genet. 2016 Jun;48(6):600-606 </Citation><ArticleIdList><ArticleId IdType="pubmed">27111033 </ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2013 Aug 22;500(7463):415-21 </Citation><ArticleIdList><ArticleId IdType="pubmed">23945592 </ArticleId></ArticleIdList></Reference><Reference><Citation>Oncotarget. 2017 Dec 16;9(4):4537-4548 </Citation><ArticleIdList><ArticleId IdType="pubmed">29435122 </ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Genet. 2011 Aug 07;43(9):875-8 </Citation><ArticleIdList><ArticleId IdType="pubmed">21822268 </ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Urol. 2017 Feb 07;14(4):215-229 </Citation><ArticleIdList><ArticleId IdType="pubmed">28169993 </ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29785026 </PMID><DateCompleted><Year>2019 </Year><Month>05 </Month><Day>13 </Day></DateCompleted><DateRevised><Year>2019 </Year><Month>12 </Month><Day>10 </Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1546-170X </ISSN><JournalIssue CitedMedium="Internet"><Volume>24 </Volume><Issue>6 </Issue><PubDate><Year>2018 </Year><Month>06 </Month></PubDate></JournalIssue><Title>Nature medicine </Title><ISOAbbreviation>Nat Med </ISOAbbreviation></Journal><ArticleTitle>Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy. </ArticleTitle><Pagination><MedlinePgn>758-769 </MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41591-018-0034-6 </ELocationID><Abstract><AbstractText>The lysine methyltransferase KMT2C (also known as MLL3), a subunit of the COMPASS complex, implements monomethylation of Lys4 on histone H3 (H3K4) at gene enhancers. KMT2C (hereafter referred to as MLL3) frequently incurs point mutations across a range of human tumor types, but precisely how these lesions alter MLL3 function and contribute to oncogenesis is unclear. Here we report a cancer mutational hotspot in MLL3 within the region encoding its plant homeodomain (PHD) repeats and demonstrate that this domain mediates association of MLL3 with the histone H2A deubiquitinase and tumor suppressor BAP1. Cancer-associated mutations in the sequence encoding the MLL3 PHD repeats disrupt the interaction between MLL3 and BAP1 and correlate with poor patient survival. Cancer cells that had PHD-associated MLL3 mutations or lacked BAP1 showed reduced recruitment of MLL3 and the H3K27 demethylase KDM6A (also known as UTX) to gene enhancers. As a result, inhibition of the H3K27 methyltransferase activity of the Polycomb repressive complex 2 (PRC2) in tumor cells harboring BAP1 or MLL3 mutations restored normal gene expression patterns and impaired cell proliferation in vivo. This study provides mechanistic insight into the oncogenic effects of PHD-associated mutations in MLL3 and suggests that restoration of a balanced state of Polycomb-COMPASS activity may have therapeutic efficacy in tumors that bear mutations in the genes encoding these epigenetic factors. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang </LastName><ForeName>Lu </ForeName><Initials>L </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao </LastName><ForeName>Zibo </ForeName><Initials>Z </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ozark </LastName><ForeName>Patrick A </ForeName><Initials>PA </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fantini </LastName><ForeName>Damiano </ForeName><Initials>D </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marshall </LastName><ForeName>Stacy A </ForeName><Initials>SA </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rendleman </LastName><ForeName>Emily J </ForeName><Initials>EJ </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cozzolino </LastName><ForeName>Kira A </ForeName><Initials>KA </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Louis </LastName><ForeName>Nundia </ForeName><Initials>N </Initials><AffiliationInfo><Affiliation>Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>He </LastName><ForeName>Xingyao </ForeName><Initials>X </Initials><AffiliationInfo><Affiliation>Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morgan </LastName><ForeName>Marc A </ForeName><Initials>MA </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Takahashi </LastName><ForeName>Yoh-Hei </ForeName><Initials>YH </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Collings </LastName><ForeName>Clayton K </ForeName><Initials>CK </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith </LastName><ForeName>Edwin R </ForeName><Initials>ER </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ntziachristos </LastName><ForeName>Panagiotis </ForeName><Initials>P </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Savas </LastName><ForeName>Jeffrey N </ForeName><Initials>JN </Initials><AffiliationInfo><Affiliation>Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou </LastName><ForeName>Lihua </ForeName><Initials>L </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hashizume </LastName><ForeName>Rintaro </ForeName><Initials>R </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meeks </LastName><ForeName>Joshua J </ForeName><Initials>JJ </Initials><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shilatifard </LastName><ForeName>Ali </ForeName><Initials>A </Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-7490-2854 </Identifier><AffiliationInfo><Affiliation>Simpson Querrey Center for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ash@northwestern.edu. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ash@northwestern.edu. </Affiliation></AffiliationInfo></Author></AuthorList><Language>eng </Language><GrantList CompleteYN="Y"><Grant><GrantID>R50 CA211428 </GrantID><Acronym>CA </Acronym><Agency>NCI NIH HHS </Agency><Country>United States </Country></Grant><Grant><GrantID>R35 CA197569 </GrantID><Acronym>CA </Acronym><Agency>NCI NIH HHS </Agency><Country>United States </Country></Grant><Grant><GrantID>R00 DC013805 </GrantID><Acronym>DC </Acronym><Agency>NIDCD NIH HHS </Agency><Country>United States </Country></Grant><Grant><GrantID>R01 NS093079 </GrantID><Acronym>NS </Acronym><Agency>NINDS NIH HHS </Agency><Country>United States </Country></Grant><Grant><GrantID>I01 BX003692 </GrantID><Acronym>BX </Acronym><Agency>BLRD VA </Agency><Country>United States </Country></Grant><Grant><GrantID>T32 CA070085 </GrantID><Acronym>CA </Acronym><Agency>NCI NIH HHS </Agency><Country>United States </Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article </PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural </PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't </PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018 </Year><Month>05 </Month><Day>21 </Day></ArticleDate></Article><MedlineJournalInfo><Country>United States </Country><MedlineTA>Nat Med </MedlineTA><NlmUniqueID>9502015 </NlmUniqueID><ISSNLinking>1078-8956 </ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="C400134">BAP1 protein, human </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D002843">Chromatin </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D004268">DNA-Binding Proteins </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="C452979">KMT2C protein, human </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D009687">Nuclear Proteins </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D063146">Polycomb-Group Proteins </NameOfSubstance></Chemical><Chemical><RegistryNumber>0 </RegistryNumber><NameOfSubstance UI="D025521">Tumor Suppressor Proteins </NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.11.- </RegistryNumber><NameOfSubstance UI="D056466">Histone Demethylases </NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.11.- </RegistryNumber><NameOfSubstance UI="C523998">KDM6A protein, human </NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.19.12 </RegistryNumber><NameOfSubstance UI="D043222">Ubiquitin Thiolesterase </NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM </CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002843" MajorTopicYN="N">Chromatin </DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004268" MajorTopicYN="N">DNA-Binding Proteins </DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry </QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics </QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004742" MajorTopicYN="Y">Enhancer Elements, Genetic </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D044127" MajorTopicYN="Y">Epigenesis, Genetic </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015972" MajorTopicYN="N">Gene Expression Regulation, Neoplastic </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D056466" MajorTopicYN="N">Histone Demethylases </DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008819" MajorTopicYN="N">Mice, Nude </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation </DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009687" MajorTopicYN="N">Nuclear Proteins </DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000075925" MajorTopicYN="N">PHD Zinc Fingers </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D063146" MajorTopicYN="N">Polycomb-Group Proteins </DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis </DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D025521" MajorTopicYN="N">Tumor Suppressor Proteins </DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D043222" MajorTopicYN="N">Ubiquitin Thiolesterase </DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism </QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017 </Year><Month>10 </Month><Day>17 </Day></PubMedPubDate><PubMedPubDate 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</ISSN><JournalIssue CitedMedium="Internet"><Volume>9 </Volume><Issue>4 </Issue><PubDate><Year>2018 </Year><Month>Jan </Month><Day>12 </Day></PubDate></JournalIssue><Title>Oncotarget </Title><ISOAbbreviation>Oncotarget </ISOAbbreviation></Journal><ArticleTitle>APOBEC-mediated mutagenesis in urothelial carcinoma is associated with improved survival, mutations in DNA damage response genes, and immune response. </ArticleTitle><Pagination><MedlinePgn>4537-4548 </MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.18632/oncotarget.23344 </ELocationID><Abstract><AbstractText>APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. We explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival using sequencing data from The Cancer Genome Atlas (<i>n </i> = 395), Beijing Genomics Institute (<i>n </i> = 99), and Cancer Cell Line Encyclopedia. Tumors were split into "APOBEC-high" and "APOBEC-low" based on APOBEC enrichment. Patients with APOBEC-high tumors have better overall survival compared to those with APOBEC-low tumors (38.2 vs. 18.5 months, <i>p </i> = 0.005). APOBEC-high tumors are more likely to have mutations in DNA damage response genes (<i>TP53, ATR, BRCA2 </i>) and chromatin regulatory genes (<i>ARID1A, MLL, MLL3 </i>), while APOBEC-low tumors are more likely to have mutations in <i>FGFR3 </i> and <i>KRAS </i>. <i>APOBEC3A </i> and <i>APOBEC3B </i> expression correlates with mutation burden, regardless of bladder tumor molecular subtype. APOBEC mutagenesis is associated with increased expression of immune signatures, including interferon signaling, and expression of <i>APOBEC3B </i> is increased after stimulation of APOBEC-high bladder cancer cell lines with IFNγ. In summary, APOBEC-high tumors are more likely to have mutations in DNA damage response and chromatin regulatory genes, potentially providing more substrate for APOBEC enzymes, leading to a hypermutational phenotype and the subsequent enhanced immune response. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Glaser </LastName><ForeName>Alexander P </ForeName><Initials>AP </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fantini </LastName><ForeName>Damiano </ForeName><Initials>D </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang </LastName><ForeName>Yiduo </ForeName><Initials>Y </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu </LastName><ForeName>Yanni </ForeName><Initials>Y </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rimar </LastName><ForeName>Kalen J </ForeName><Initials>KJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Podojil </LastName><ForeName>Joseph R </ForeName><Initials>JR </Initials><AffiliationInfo><Affiliation>Interdepartmental Immunobiology Center, Department of Microbiology-Immunology, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miller </LastName><ForeName>Stephen D </ForeName><Initials>SD </Initials><AffiliationInfo><Affiliation>Interdepartmental Immunobiology Center, Department of Microbiology-Immunology, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meeks </LastName><ForeName>Joshua J </ForeName><Initials>JJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author></AuthorList><Language>eng </Language><GrantList CompleteYN="Y"><Grant><GrantID>I01 BX003692 </GrantID><Acronym>BX </Acronym><Agency>BLRD VA </Agency><Country>United States </Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article </PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017 </Year><Month>12 </Month><Day>16 </Day></ArticleDate></Article><MedlineJournalInfo><Country>United States </Country><MedlineTA>Oncotarget </MedlineTA><NlmUniqueID>101532965 </NlmUniqueID><ISSNLinking>1949-2553 </ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">APOBEC deaminases </Keyword><Keyword MajorTopicYN="N">DNA damage </Keyword><Keyword MajorTopicYN="N">interferon </Keyword><Keyword MajorTopicYN="N">mutagenesis </Keyword><Keyword MajorTopicYN="N">urinary bladder neoplasms </Keyword></KeywordList><CoiStatement>CONFLICTS OF INTEREST The authors declare no competing interest. </CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017 </Year><Month>09 </Month><Day>13 </Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017 </Year><Month>11 </Month><Day>26 </Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018 </Year><Month>2 </Month><Day>14 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018 </Year><Month>2 </Month><Day>13 </Day><Hour>6 </Hour><Minute>0 </Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018 </Year><Month>2 </Month><Day>13 </Day><Hour>6 </Hour><Minute>1 </Minute></PubMedPubDate></History><PublicationStatus>epublish </PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">29435122 </ArticleId><ArticleId IdType="doi">10.18632/oncotarget.23344 </ArticleId><ArticleId IdType="pii">23344 </ArticleId><ArticleId 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Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rimar </LastName><ForeName>Kalen J </ForeName><Initials>KJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang </LastName><ForeName>Yiduo </ForeName><Initials>Y </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schipma </LastName><ForeName>Matthew </ForeName><Initials>M </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Varghese </LastName><ForeName>Nobish </ForeName><Initials>N </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rademaker </LastName><ForeName>Alfred </ForeName><Initials>A </Initials><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Behdad </LastName><ForeName>Amir </ForeName><Initials>A </Initials><AffiliationInfo><Affiliation>Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yellapa </LastName><ForeName>Aparna </ForeName><Initials>A </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu </LastName><ForeName>Yanni </ForeName><Initials>Y </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sze </LastName><ForeName>Christie Ching-Lin </ForeName><Initials>CC </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang </LastName><ForeName>Lu </ForeName><Initials>L </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao </LastName><ForeName>Zibo </ForeName><Initials>Z </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Crawford </LastName><ForeName>Susan E </ForeName><Initials>SE </Initials><AffiliationInfo><Affiliation>Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu </LastName><ForeName>Deqing </ForeName><Initials>D </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Licht </LastName><ForeName>Jonathan D </ForeName><Initials>JD </Initials><AffiliationInfo><Affiliation>Department of Medicine, Division of Hematology and Oncology, University of Florida, Gainesville, FL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Collings </LastName><ForeName>Clayton K </ForeName><Initials>CK </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bartom </LastName><ForeName>Elizabeth </ForeName><Initials>E </Initials><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Theodorescu </LastName><ForeName>Dan </ForeName><Initials>D </Initials><AffiliationInfo><Affiliation>Department of Surgery (Urology) and Pharmacology, Comprehensive Cancer Center, University of Colorado, Denver, CO, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shilatifard </LastName><ForeName>Ali </ForeName><Initials>A </Initials><AffiliationInfo><Affiliation>Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. </Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meeks </LastName><ForeName>Joshua J </ForeName><Initials>JJ </Initials><AffiliationInfo><Affiliation>Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. joshua.meeks@northwestern.edu. </Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Robert H. 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