Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion

被引：239

作者：

Bass, Adam J. ^{[1
,2
,3
,4
]}

Lawrence, Michael S. ^{[1
]}

Brace, Lear E. ^{[2
]}

Ramos, Alex H. ^{[1
,2
]}

Drier, Yotam ^{[5
]}

Cibulskis, Kristian ^{[1
]}

Sougnez, Carrie ^{[1
]}

Voet, Douglas ^{[1
]}

Saksena, Gordon ^{[1
]}

Sivachenko, Andrey ^{[1
]}

Jing, Rui ^{[1
]}

Parkin, Melissa ^{[1
]}

Pugh, Trevor ^{[1
,2
]}

Verhaak, Roel G. ^{[1
,2
]}

Stransky, Nicolas ^{[1
]}

Boutin, Adam T. ^{[2
]}

Barretina, Jordi ^{[1
]}

Solit, David B. ^{[6
]}

Vakiani, Evi ^{[7
]}

Shao, Wenlin ^{[8
]}

Mishina, Yuji ^{[8
]}

Warmuth, Markus ^{[8
]}

Jimenez, Jose ^{[9
]}

Chiang, Derek Y. ^{[10
]}

Signoretti, Sabina ^{[11
,12
]}

Kaelin, William G., Jr. ^{[2
,3
]}

Spardy, Nicole ^{[2
]}

Hahn, William C. ^{[1
,2
,3
,4
]}

Hoshida, Yujin ^{[1
]}

Ogino, Shuji ^{[2
,11
,12
,13
]}

DePinho, Ronald A. ^{[2
,3
,14
,15
]}

Chin, Lynda ^{[1
,2
,16
]}

Garraway, Levi A. ^{[1
,2
,3
,4
]}

Fuchs, Charles S. ^{[2
,3
,13
]}

Baselga, Jose ^{[9
,17
]}

Tabernero, Josep ^{[9
]}

Gabriel, Stacey ^{[1
]}

Lander, Eric S. ^{[1
,18
,19
]}

Getz, Gad ^{[1
]}

Meyerson, Matthew ^{[1
,2
,4
,11
]}

机构：

[1] Broad Inst, Cambridge, MA USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[4] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[5] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel

[6] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA

[7] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA

[8] Novartis Inst Biomed Res, Cambridge, MA USA

[9] Hosp Valle De Hebron, Dept Med Oncol, Barcelona, Spain

[10] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[11] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[12] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[13] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA

[14] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[15] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA

[16] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA

[17] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA

[18] MIT, Cambridge, MA 02139 USA

[19] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 10期

基金：

美国国家卫生研究院;

关键词：

HUMAN BREAST; TUMOR-SUPPRESSOR; PROSTATE-CANCER; LUNG-CANCER; GENES; COMPLEX; RISK; CHROMOSOME-5Q21; TUMORIGENESIS; REARRANGEMENT;

D O I：

10.1038/ng.936

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma(1) and have surveyed exons of protein-coding genes for mutations in 11 affected individuals(2,3). Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7x and 31.9x coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted inframe fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with beta-catenin(4) in colorectal carcinogenesis(5,6), the fusion lacks the TCF4 beta-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events.

引用

页码：964 / U67

页数：7

共 39 条

[21] The mutation spectrum revealed by paired genome sequences from a lung cancer patient
Lee, William
Jiang, Zhaoshi
Liu, Jinfeng
Haverty, Peter M.
Guan, Yinghui
Stinson, Jeremy
Yue, Peng
Zhang, Yan
Pant, Krishna P.
Bhatt, Deepali
Ha, Connie
Johnson, Stephanie
Kennemer, Michael I.
Mohan, Sankar
Nazarenko, Igor
Watanabe, Colin
Sparks, Andrew B.
Shames, David S.
Gentleman, Robert
de Sauvage, Frederic J.
Stern, Howard
Pandita, Ajay
Ballinger, Dennis G.
Drmanac, Radoje
Modrusan, Zora
Seshagiri, Somasekar
Zhang, Zemin
[J]. NATURE, 2010, 465 (7297) : 473 - 477
[22] The first human acute myeloid leukemia genome ever fully sequenced
Falini, Brunangelo
[J]. HAEMATOLOGICA, 2024, 109 (01) : 1 - 2
[23] Molecular Origins of Cancer: Molecular Basis of Colorectal Cancer.
Markowitz, Sanford D.
Bertagnolli, Monica M.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (25) : 2449 - 2460
[24] A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen
Moffat, J
Grueneberg, DA
Yang, XP
Kim, SY
Kloepfer, AM
Hinkle, G
Piqani, B
Eisenhaure, TM
Luo, B
Grenier, JK
Carpenter, AE
Foo, SY
Stewart, SA
Stockwell, BR
Hacohen, N
Hahn, WC
Lander, ES
Sabatini, DM
Root, DE
[J]. CELL, 2006, 124 (06) : 1283 - 1298
[25] MUTATIONS OF CHROMOSOME-5Q21 GENES IN FAP AND COLORECTAL-CANCER PATIENTS
NISHISHO, I
NAKAMURA, Y
MIYOSHI, Y
MIKI, Y
ANDO, H
HORII, A
KOYAMA, K
UTSUNOMIYA, J
BABA, S
HEDGE, P
MARKHAM, A
KRUSH, AJ
PETERSEN, G
HAMILTON, SR
NILBERT, MC
LEVY, DB
BRYAN, TM
PREISINGER, AC
SMITH, KJ
SU, LK
KINZLER, KW
VOGELSTEIN, B
[J]. SCIENCE, 1991, 253 (5020) : 665 - 669
[26] Molecular classification and correlates in colorectal cancer
Ogino, Shuji
Goel, Ajay
[J]. JOURNAL OF MOLECULAR DIAGNOSTICS, 2008, 10 (01) : 13 - 27
[27] A comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, Erin D.
Cheetham, R. Keira
Stephens, Philip J.
McBride, David J.
Humphray, Sean J.
Greenman, Chris D.
Varela, Ignacio
Lin, Meng-Lay
Ordonez, Gonzalo R.
Bignell, Graham R.
Ye, Kai
Alipaz, Julie
Bauer, Markus J.
Beare, David
Butler, Adam
Carter, Richard J.
Chen, Lina
Cox, Anthony J.
Edkins, Sarah
Kokko-Gonzales, Paula I.
Gormley, Niall A.
Grocock, Russell J.
Haudenschild, Christian D.
Hims, Matthew M.
James, Terena
Jia, Mingming
Kingsbury, Zoya
Leroy, Catherine
Marshall, John
Menzies, Andrew
Mudie, Laura J.
Ning, Zemin
Royce, Tom
Schulz-Trieglaff, Ole B.
Spiridou, Anastassia
Stebbings, Lucy A.
Szajkowski, Lukasz
Teague, Jon
Williamson, David
Chin, Lynda
Ross, Mark T.
Campbell, Peter J.
Bentley, David R.
Futreal, P. Andrew
Stratton, Michael R.
[J]. NATURE, 2010, 463 (7278) : 191 - U73
[28] The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer
Pomerantz, Mark M.
Ahmadiyeh, Nasim
Jia, Li
Herman, Paula
Verzi, Michael P.
Doddapaneni, Harshavardhan
Beckwith, Christine A.
Chan, Jennifer A.
Hills, Adam
Davis, Matt
Yao, Keluo
Kehoe, Sarah M.
Lenz, Heinz-Josef
Haiman, Christopher A.
Yan, Chunli
Henderson, Brian E.
Frenkel, Baruch
Barretina, Jordi
Bass, Adam
Tabernero, Josep
Baselga, Jose
Regan, Meredith M.
Manak, J. Robert
Shivdasani, Ramesh
Coetzee, Gerhard A.
Freedman, Matthew L.
[J]. NATURE GENETICS, 2009, 41 (08) : 882 - 884
[29] Synergy between tumor suppressor APC and the β-catenin-Tcf4 target Tcf1
Roose, J
Huls, G
van Beest, M
Moerer, P
van der Horn, K
Goldschmeding, R
Logtenberg, T
Clevers, H
[J]. SCIENCE, 1999, 285 (5435) : 1923 - 1926
[30] The consensus coding sequences of human breast and colorectal cancers
Sjoeblom, Tobias
Jones, Sian
Wood, Laura D.
Parsons, D. Williams
Lin, Jimmy
Barber, Thomas D.
Mandelker, Diana
Leary, Rebecca J.
Ptak, Janine
Silliman, Natalie
Szabo, Steve
Buckhaults, Phillip
Farrell, Christopher
Meeh, Paul
Markowitz, Sanford D.
Willis, Joseph
Dawson, Dawn
Willson, James K. V.
Gazdar, Adi F.
Hartigan, James
Wu, Leo
Liu, Changsheng
Parmigiani, Giovanni
Park, Ben Ho
Bachman, Kurtis E.
Papadopoulos, Nickolas
Vogelstein, Bert
Kinzler, Kenneth W.
Velculescu, Victor E.
[J]. SCIENCE, 2006, 314 (5797) : 268 - 274

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