Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A - TCF7L2 fusion
Adam J. Bass,Adam J. Bass,Michael S. Lawrence,Lear E. Brace,Alex H. Ramos,Alex H. Ramos,Yotam Drier,Kristian Cibulskis,Carrie Sougnez,Douglas Voet,Gordon Saksena,Andrey Sivachenko,Rui Jing,Melissa Parkin,Trevor J. Pugh,Trevor J. Pugh,Roel G.W. Verhaak,Nicolas Stransky,Adam T. Boutin,Jordi Barretina,David B. Solit,Evi Vakiani,Wenlin Shao,Yuji Mishina,Markus Warmuth,Jose Jimenez,Derek Y. Chiang,Sabina Signoretti,William G. Kaelin,Nicole Spardy,William C. Hahn,William C. Hahn,Yujin Hoshida,Shuji Ogino,Ronald A. DePinho,Lynda Chin,Levi A. Garraway,Levi A. Garraway,Charles S. Fuchs,Jose Baselga,Jose Baselga,Josep Tabernero,Stacey Gabriel,Eric S. Lander,Eric S. Lander,Gad Getz,Matthew Meyerson,Matthew Meyerson +47 more
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TLDR
Previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events are shown.Abstract:
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. 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 30.7× and 31.9× 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 in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-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.read more
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Comprehensive molecular characterization of human colon and rectal cancer
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TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
Journal ArticleDOI
Integrated genomic analyses of ovarian carcinoma
Debra A. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,M. Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Beth Y. Karlan,Douglas A. Levine,Douglas A. Levine,Douglas A. Levine,Gordon B. Mills,Gordon B. Mills,Carl Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,J. A. Drummond,G. Fowler,Preethi H. Gunaratne,A. C. Hawes,C. L. Kovar,L. R. Lewis,M. B. Morgan,I. F. Newsham,J. Santibanez,Jeffrey G. Reid,L. R. Trevino,Yue Wu,M. Wang,Donna M. Muzny,D. A. Wheeler,Richard A. Gibbs,Gad Getz,Gad Getz,Michael S. Lawrence,Michael S. Lawrence,Kristian Cibulskis,Kristian Cibulskis,Andrey Sivachenko,C. Sougnez,Douglas Voet,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,Kristin G. Ardlie,T. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,M. O'Laughlin,D. J. Dooling,Linnea Fulton,R. Abbott,N. D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Hayden R. Schmidt,Joelle Kalicki,K. D. Delehaunty,Catrina Fronick,Ryan Demeter,L. Cook,J. W. Wallis,L. Lin,Vincent Magrini,J. S. Hodges,James M. Eldred,S. M. Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,R. G.W. Verhaak,Suzie Carter,Craig H. Mermel,G. Saksena,G. Saksena,H. Nguyen,R. C. Onofrio,D. Hubbard,S. Gupta,A. Crenshaw,A. H. Ramos,Lynda Chin,Lynda Chin,Alexei Protopopov,Jinghui Zhang,Jinghui Zhang,Jinghui Zhang,T. M. Kim,Ilana Perna,Y. Xiao,Hailei Zhang,Gang Ren,N. Sathiamoorthy,R. W. Park,R. W. Park,Eunjung Lee,Peter J. Park,Peter J. Park,Raju Kucherlapati,D. M. Absher,L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,L. Cope,James G. Herman,H. Shen,Daniel J. Weisenberger,Houtan Noushmehr,F. Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,J. Buckley,Stephen B. Baylin,Paul T. Spellman,Paul T. Spellman,Elizabeth Purdom,Pierre Neuvial,Pierre Neuvial,Henrik Bengtsson,Henrik Bengtsson,L. R. Jakkula,S. Durinck,S. Durinck,Junhong Han,Junhong Han,S. Dorton,H. Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,J. G. Conboy,Bahram Parvin,H. S. Feiler,Terence P. Speed,Joe W. Gray,Joe W. Gray,N. D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Nikolaus Schultz,L. Borsu,Alex E. Lash,Cameron Brennan,A. Viale,Chris Sander,M. Ladanyi,M. Ladanyi,Katherine A. Hoadley,Katherine A. Hoadley,S. Meng,Y. Du,Y. Du,Yigong Shi,Lulin Li,Y. J. Turman,D. Zang,E. B. Helms,S. Balu,Xiang Zhou,Jane Y. Wu,M. D. Topal,D. N. Hayes,D. N. Hayes,Charles M. Perou,Chaowei Wu,S. Shukla,A. Sivachenko,R. Jing,Yingkai Liu,M. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,A. Olshen,B. Reva,Yevgeniy Antipin,R. Shen,P. Mankoo,Robert L. Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Z. Sanborn,Charles J. Vaske,Jieqing Zhu,Christopher Szeto,G. K. Scott,Christina Yau,Matthew D. Wilkerson,N. Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,T. Shelton,Dirk Grimm,Martha Hatfield,Scott Morris,P. Yena,P. Rhodes,Mark E. Sherman,J. Paulauskis,S. Millis,A. Kahn,John M. Greene,R. Sfeir,M. A. Jensen,John W. Chen,J. Whitmore,S. Alonso,J. Jordan,A. Chu,A. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jane Peterson,Elizabeth J. Thomson +285 more
TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
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