{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu"],"funding":["Cancer Research UK","Pancreatic Cancer UK","Medical Research Council","NHGRI NIH HHS","NCI NIH HHS","Wellcome Trust"],"pagination":["185-203.e13"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5964983"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(2)"],"pubmed_abstract":["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."],"journal":["Cancer cell"],"pubmed_title":["Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma."],"pmcid":["PMC5964983"],"funding_grant_id":["23526","17263","U24 CA143867","U24 CA143845","U24 CA143848","U54 HG003273","103721/Z/14/Z","K08 CA218420","U24 CA210949","R01 CA180776","U54 HG003079","MR/N005813/1","P50 CA062924","P30 CA016086","U24 CA143866","U24 CA143843","U24 CA143882","U24 CA143840","U24 CA143883","U24 CA143835","FLF2015_04_GLASGOW","U24 CA143858","U54 HG003067","R01 CA199064","U24 CA210957","U24 CA210999","U24 CA210974","R01 HG007069","P30 CA016672","U24 CA211000","U24 CA143799","P50 CA127003","U24 CA144025"],"pubmed_authors":["Lin P","Moore RA","Bahary N","Perou CM","Lyadov V","Schumacher SE","Lawrence MS","Breggia A","Su T","Bathe O","Shroff RT","Roggin K","Gastier-Foster JM","Slotta-Huspenina J","Hibshoosh H","Rosenberg M","Pantazi A","Gibb EA","Gerken M","Chin L","Kemp R","Maithel S","Hwang RF","Ally A","Kucherlapati M","Leraas KM","Sofia HJ","Kucherlapati R","Sipahimalani P","Pretti da Cunha Tirapelli D","Sicotte H","Bailey P","Meng S","Bartlett J","Leshchiner I","Dhir R","Senbabaoglu Y","Van Den Berg DJ","Korkut A","Marra MA","Jenkins R","Manikhas G","Howard Z","Aguirre AJ","Reardon B","Roach J","Becker KF","Wong T","Voet D","Zhang JJ","Van Allen E","Noble MS","Furth E","Rathmell WK","Smyrk T","Balu S","Berrios M","Hayes DN","Zmuda E","Laird PW","Singhi AD","Kasaian K","Weisenberger DJ","Frick J","Mills GB","Gill A","Bootwalla MS","Tse K","Hoyle AP","Jefferys SR","Cibulskis C","Tavobilov M","Kim SH","Ferguson ML","Urbanski S","Sander C","Leiserson MDM","Skelly T","Livitz D","Biankin A","Gupta M","Paul D","Sebastiao Dos Santos J","McWilliams R","Mose LE","Goldenberg A","Ramirez NC","Huelsenbeck-Dill L","Tempero M","Paulauskis J","Cherniack AD","Amundadottir LT","Yeh JJ","Jennifer S","Bowen J","Liu J","Mallery D","Ramalingam S","Carlsen R","Soloway MG","Ma Y","Petersen G","Beroukhim R","Simons JV","Liu Y","Morris S","Xi L","Saksena G","Bowlby R","Mieczkowski PA","Gehlenborg N","Renkel J","Sullivan T","Oberg A","Schein JE","Crain D","Kwon SY","Balasundaram M","Gingras MC","Lolla L","Bennett J","Londin ER","Zhang W","Albert M","Shih J","Radenbaugh A","Bardeesy N","Carlotti Junior CG","Shabunin A","Murray BA","Collisson E","Zhang H","Wheeler DA","Wan Y","Shelton T","Zhang L","Shen H","Shi Y","Boice L","Setdikova G","Lai PH","Sepulveda A","Burks E","Cancer Genome Initiative Apgi AP","Stewart C","Gabriel SB","Raphael BJ","Behera M","Kamburov A","Felau I","Paklina O","Johns A","Birol I","Potapova O","Eschbacher J","Maglinte DT","Zuna R","Penny R","Shelton C","Triche TJ","Meier S","Hutter CM","Burch P","Osunkoya A","Kim H","Parker JS","Cancer Genome Atlas Research Network","Kim J","Chuah E","Kim P","Lichtenberg TM","Sekhon H","Lee D","Cancer Genome Atlas Research Network. 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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.","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Aug","modification":"2020-10-29T11:29:01Z","creation":"2019-03-26T23:50:40Z"},"accession":"S-EPMC5964983","cross_references":{"pubmed":["28810144"],"doi":["10.1016/j.ccell.2017.07.007"]}}