Comprehensive molecular characterization of human colon and rectal cancer

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Title
Comprehensive molecular characterization of human colon and rectal cancer
Author
Muzny, Donna M.Bainbridge, Matthew N.Chang, KyleDinh, Huyen H.Drummond, Jennifer A.Fowler, GeraldKovar, Christie L.Lewis, Lora R.Morgan, Margaret B.Newsham, Irene F.Reid, Jeffrey G.Santibanez, JirehShinbrot, EveTrevino, Lisa R.Wu, Yuan-QingWang, MinGunaratne, PreethiDonehower, Lawrence A.Creighton, Chad J.Wheeler, David A.Gibbs, Richard A.Lawrence, Michael S.Voet, DouglasJing, RuiCibulskis, KristianSivachenko, AndreyStojanov, PetarMcKenna, AaronLander, Eric S.Gabriel, StaceyGetz, GadDing, LiFulton, Robert S.Koboldt, Daniel C.Wylie, ToddWalker, JasonDooling, David J.Fulton, LucindaDelehaunty, Kim D.Fronick, Catrina C.Demeter, RyanMardis, Elaine R.Wilson, Richard K.Chu, AndyChun, Hye-Jung E.Mungall, Andrew J.Pleasance, ErinRobertson, A. GordonStoll, DominikBalasundaram, MirunaBirol, InancButterfield, Yaron S. N.Chuah, EricCoope, Robin J. N.Dhalla, NoreenGuin, RanabirHirst, CarrieHirst, MartinHolt, Robert A.Lee, DarleneLi, Haiyan I.Mayo, MichaelMoore, Richard A.Schein, Jacqueline E.Slobodan, Jared R.Tam, AngelaThiessen, NinaVarhol, RichardZeng, ThomasZhao, YongjunJones, Steven J. M.Marra, Marco A.Bass, Adam J.Ramos, Alex H.Saksena, GordonCherniack, Andrew D.Schumacher, Stephen E.Tabak, BarbaraCarter, Scott L.Pho, Nam H.Nguyen, HuyOnofrio, Robert C.Crenshaw, AndrewArdlie, KristinBeroukhim, RameenWinckler, WendyGetz, GadMeyerson, MatthewProtopopov, AlexeiZhang, JuinhuaHadjipanayis, AngelaLee, EunjungXi, RuibinYang, LixingRen, XiaojiaZhang, HaileiSathiamoorthy, NarayananShukla, SachetChen, Peng-ChiehHaseley, PsalmXiao, YonghongLee, SeminSeidman, JonathanChin, LyndaPark, Peter J.Kucherlapati, RajuAuman, J. ToddHoadley, Katherine A.Du, YingWilkerson, Matthew D.Shi, YanLiquori, ChristinaMeng, ShaowuLi, LingTurman, Yidi J.Topal, Michael D.Tan, DonghuiWaring, ScotBuda, ElizabethWalsh, JesseJones, Corbin D.Mieczkowski, Piotr A.Singh, DarshanWu, JunyuanGulabani, AnishaDolina, PeterBodenheimer, TomHoyle, Alan P.Simons, Janae V.Soloway, MatthewMose, Lisle E.Jefferys, Stuart R.Balu, SaianandO'Connor, Brian D.Prins, Jan F.Chiang, Derek Y.Hayes, D. NeilPerou, Charles M.Hinoue, ToshinoriWeisenberger, Daniel J.Maglinte, Dennis T.Pan, FeiBerman, Benjamin P.Van den Berg, David J.Shen, HuiJr, Timothy TricheBaylin, Stephen B.Laird, Peter W.Getz, GadNoble, MichaelVoet, DougSaksena, GordonGehlenborg, NilsDiCara, DanielZhang, JuinhuaZhang, HaileiWu, Chang-JiunLiu, Spring YingchunShukla, SachetLawrence, Michael S.Zhou, LihuaSivachenko, AndreyLin, PeiStojanov, PetarJing, RuiPark, Richard W.Nazaire, Marc-DanieRobinson, JimThorvaldsdottir, HelgaMesirov, JillPark, Peter J.Chin, LyndaThorsson, VesteinnReynolds, Sheila M.Bernard, BradyKreisberg, RichardLin, JakeIype, LisaBressler, RyanErkkilae, TimoGundapuneni, MadhumatiLiu, YuexinNorberg, AdamRobinson, TomDa YangZhang, WeiShmulevich, IlyaDe Ronde, Jorma J.Schultz, NikolausCerami, EthanCiriello, GiovanniGoldberg, Arthur P.Gross, BenjaminJacobsen, AndersGao, JianjiongKaczkowski, BogumilSinha, RileenAksoy, B. ArmanAntipin, YevgeniyReva, BorisShen, RonglaiTaylor, Barry S.Chan, Timothy A.Ladanyi, MarcSander, ChrisAkbani, RehanZhang, NianxiangBroom, Bradley M.Casasent, TodUnruh, AnnaWakefield, ChrisHamilton, Stanley R.Cason, R. CraigBaggerly, Keith A.Weinstein, John N.Haussler, DavidBenz, Christopher C.Stuart, Joshua M.Benz, Stephen C.Sanborn, J. ZacharyVaske, Charles J.Zhu, JingchunSzeto, ChristopherScott, Gary K.Yau, ChristinaNg, SamGoldstein, TedEllrott, KyleCollisson, EricCozen, Aaron E.Zerbino, DanielWilks, ChristopherCraft, BrianSpellman, PaulPenny, RobertShelton, TroyHatfield, MarthaMorris, ScottYena, PeggyShelton, CandaceSherman, MarkPaulauskis, JosephGastier-Foster, Julie M.Bowen, JayRamirez, Nilsa C.Black, AaronPyatt, RobertWise, LisaWhite, PeterBertagnolli, MonicaBrown, JenChan, Timothy A.Chu, Gerald C.Czerwinski, ChristineDenstman, FredDhir, RajivDoerner, ArnulfFuchs, Charles S.Guillem, Jose G.Iacocca, MaryJuhl, HartmutKaufman, AndrewKohl, Bernard, IIIVan Le, XuanMariano, Maria C.Medina, Elizabeth N.Meyers, MichaelNash, Garrett M.Paty, Phillip B.Petrelli, NicholasRabeno, BrendaRichards, William G.Solit, DavidSwanson, PatTemple, LarissaTepper, Joel E.Thorp, RichardVakiani, EfseviaWeiser, Martin R.Willis, Joseph E.Witkin, GaryZeng, ZhaoshiZinner, Michael J.Zornig, CarstenJensen, Mark A.Sfeir, RobertKahn, Ari B.Chu, Anna L.Kothiyal, PrachiWang, ZhiningSnyder, Eric E.Pontius, JoanPihl, Todd D.Ayala, BrendaBackus, MarkWalton, JessicaWhitmore, JonBaboud, JulienBerton, Dominique L.Nicholls, Matthew C.Srinivasan, DeepakRaman, RohiniGirshik, StanleyKigonya, Peter A.Alonso, ShelleySanbhadti, Rashmi N.Barletta, Sean P.Greene, John M.Pot, David A.Shaw, Kenna R. MillsDillon, Laura A. L.Buetow, KenDavidsen, TanjaDemchok, John A.Eley, GregFerguson, MartinFielding, PeterSchaefer, CarlSheth, MargiYang, LimingGuyer, Mark S.Ozenberger, Bradley A.Palchik, Jacqueline D.Peterson, JaneSofia, Heidi J.Thomson, Elizabeth
Keywords
COLORECTAL-CANCER; INTESTINAL EPITHELIUM; SOMATIC MUTATIONS; HUMAN BREAST; WILMS-TUMOR; GENE; DIFFERENTIATION; ONCOGENE; CELLS; WTX
Issue Date
2012-07
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE, v.487, no.7407, pp.330 - 337
Abstract
To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression
URI
Go to Link
DOI
10.1038/nature11252
ISSN
0028-0836
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SLS_Journal Papers
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