biostudies-literatureCancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.eduCancer Research UKPancreatic Cancer UKMedical Research CouncilNHGRI NIH HHSNCI NIH HHSWellcome Trust185-203.e13https://www.ebi.ac.uk/biostudies/studies/S-EPMC5964983biostudies-literatureUnknown32(2)We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGF?R2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.Cancer cellIntegrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.PMC59649832352617263U24 CA143867U24 CA143845U24 CA143848U54 HG003273103721/Z/14/ZK08 CA218420U24 CA210949R01 CA180776U54 HG003079MR/N005813/1P50 CA062924P30 CA016086U24 CA143866U24 CA143843U24 CA143882U24 CA143840U24 CA143883U24 CA143835FLF2015_04_GLASGOWU24 CA143858U54 HG003067R01 CA199064U24 CA210957U24 CA210999U24 CA210974R01 HG007069P30 CA016672U24 CA211000U24 CA143799P50 CA127003U24 CA144025Lin PMoore RABahary NPerou CMLyadov VSchumacher SELawrence MSBreggia ASu TBathe OShroff RTRoggin KGastier-Foster JMSlotta-Huspenina JHibshoosh HRosenberg MPantazi AGibb EAGerken MChin LKemp RMaithel SHwang RFAlly AKucherlapati MLeraas KMSofia HJKucherlapati RSipahimalani PPretti da Cunha Tirapelli DSicotte HBailey PMeng SBartlett JLeshchiner IDhir RSenbabaoglu YVan Den Berg DJKorkut AMarra MAJenkins RManikhas GHoward ZAguirre AJReardon BRoach JBecker KFWong TVoet DZhang JJVan Allen ENoble MSFurth ERathmell WKSmyrk TBalu SBerrios MHayes DNZmuda ELaird PWSinghi ADKasaian KWeisenberger DJFrick JMills GBGill ABootwalla MSTse KHoyle APJefferys SRCibulskis CTavobilov MKim SHFerguson MLUrbanski SSander CLeiserson MDMSkelly TLivitz DBiankin AGupta MPaul DSebastiao Dos Santos JMcWilliams RMose LEGoldenberg ARamirez NCHuelsenbeck-Dill LTempero MPaulauskis JCherniack ADAmundadottir LTYeh JJJennifer SBowen JLiu JMallery DRamalingam SCarlsen RSoloway MGMa YPetersen GBeroukhim RSimons JVLiu YMorris SXi LSaksena GBowlby RMieczkowski PAGehlenborg NRenkel JSullivan TOberg ASchein JECrain DKwon SYBalasundaram MGingras MCLolla LBennett JLondin ERZhang WAlbert MShih JRadenbaugh ABardeesy NCarlotti Junior CGShabunin AMurray BACollisson EZhang HWheeler DAWan YShelton TZhang LShen HShi YBoice LSetdikova GLai PHSepulveda ABurks ECancer Genome Initiative Apgi APStewart CGabriel SBRaphael BJBehera MKamburov AFelau IPaklina OJohns ABirol IPotapova OEschbacher JMaglinte DTZuna RPenny RShelton CTriche TJMeier SHutter CMBurch POsunkoya AKim HParker JSCancer Genome Atlas Research NetworkKim JChuah EKim PLichtenberg TMSekhon HLee DCancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.eduSherman MChu AJanssen KPHolt RARieger-Christ KSaller CTepper JJones SJMChang DRigoutsos ILing SAdsay VSpellman PTLander EKarpov ASwanson PWilkerson MDJones CDSadeghi SMungall KLTam AGardner JMontgomery EMoffitt RATarvin KDemchok JAClarke AChaffee KThiessen NZenklusen JCKlimstra DWise LMayo MTarnuzzer RHess JLu YHuang MKench JStephen YJudy MMahurkar SHan SSBrooks DVoronina OPostier RSun QWang TMills Shaw KRHolbrook AAkbani RWang ZWu YTelonis AGMezlini AMMungall AJChabot JYang LTiao GTan DNaresh ROwonikoko TPark PHinoue TPihl TNoushmehr HHruban RHDhalla NGrimmond SBodenheimer TBergelson LBaylin SBMeyerson MChudamani SDefreitas TFrazer SVeluvolu URobertson AGGetz GHoadley KAPerou AHAuman JTSheth MCho JKim YHPark SJWeinstein JNSica GFei SSDubina MYena PLoher PThorne LBCurley ELau KHeiman DIfalseIntegrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGF?R2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.2017-01-01T00:00:00Z2017 Aug2020-10-29T11:29:01Z2019-03-26T23:50:40ZS-EPMC59649832881014410.1016/j.ccell.2017.07.007