Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes

被引：199

作者：

Wang, Yi Kan ^{[1
]}

Bashashati, Ali ^{[1
]}

Anglesio, Michael S. ^{[2
,3
]}

Cochrane, Dawn R. ^{[1
]}

Grewal, Diljot S. ^{[1
,2
]}

Ha, Gavin ^{[1
,14
,15
]}

McPherson, Andrew ^{[1
,2
]}

Horlings, Hugo M. ^{[1
]}

Senz, Janine ^{[1
]}

Prentice, Leah M. ^{[1
]}

Karnezis, Anthony N. ^{[2
]}

Lai, Daniel ^{[1
]}

Aniba, Mohamed R. ^{[1
]}

Zhang, Allen W. ^{[1
,4
,5
]}

Shumansky, Karey ^{[1
]}

Siu, Celia ^{[1
]}

Wan, Adrian ^{[1
]}

McConechy, Melissa K. ^{[2
]}

Li-Chang, Hector ^{[2
]}

Tone, Alicia ^{[2
,16
]}

Provencher, Diane ^{[6
,7
,8
]}

de Ladurantaye, Manon ^{[6
,7
]}

Fleury, Hubert ^{[6
,7
]}

Okamoto, Aikou ^{[9
]}

Yanagida, Satoshi ^{[9
]}

Yanaihara, Nozomu ^{[9
]}

Saito, Misato ^{[9
]}

Mungall, Andrew J. ^{[10
]}

Moore, Richard ^{[10
]}

Marra, Marco A. ^{[10
,11
]}

Gilks, C. Blake ^{[2
,12
]}

Mes-Masson, Anne-Marie ^{[6
,7
,13
]}

McAlpine, Jessica N. ^{[3
]}

Aparicio, Samuel ^{[1
,2
]}

Huntsman, David G. ^{[1
,2
,3
]}

Shah, Sohrab P. ^{[1
,2
,10
]}

机构：

[1] BC Canc Agcy, Dept Mol Oncol, Vancouver, BC, Canada

[2] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada

[3] Univ British Columbia, Dept Gynecol & Obstet, Vancouver, BC, Canada

[4] Univ British Columbia, Grad Bioinformat Training Program, Vancouver, BC, Canada

[5] Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC, Canada

[6] CRCHUM, Montreal, PQ, Canada

[7] Inst Canc Montreal, Montreal, PQ, Canada

[8] Univ Montreal, Div Gynecol Oncol, Montreal, PQ, Canada

[9] Jikei Univ, Sch Med, Dept Obstet & Gynecol, Tokyo, Japan

[10] BC Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada

[11] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[12] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC, Canada

[13] Univ Montreal, Dept Med, Montreal, PQ, Canada

[14] Dana Farber Canc Inst, Boston, MA 02115 USA

[15] Broad Inst, Boston, MA USA

[16] Princess Margaret Canc Ctr, Div Gynecol Oncol, Toronto, ON, Canada

来源：

NATURE GENETICS | 2017年 / 49卷 / 06期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院; 加拿大创新基金会;

关键词：

OLAPARIB MAINTENANCE THERAPY; MUTATIONAL PROCESSES; DIVERSE MECHANISMS; CARCINOMA; TUMORS; ENDOMETRIOSIS; MICROHOMOLOGY; EVOLUTION; RECURRENT; PATTERNS;

D O I：

10.1038/ng.3849

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival. This finding was recapitulated in two independent cohorts (n = 576 cases), transcending BRCA1 and BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped according to APOBEC deamination (26%) and age-related mutational signatures (40%). ENOCs were divided by cases with microsatellite instability (28%), with a distinct mismatch-repair mutation signature. Taken together, our work establishes the potency of the somatic genome, reflective of diverse DNA repair deficiencies, to stratify ovarian cancers into distinct biological strata within the major histotypes.

引用

页码：856 / +

页数：11

共 51 条

[1] Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary [J].

Ahmed, Ashour Ahmed ;

Etemadmoghadam, Dariush ;

Temple, Jillian ;

Lynch, Andy G. ;

Riad, Mohamed ;

Sharma, Raghwa ;

Stewart, Colin ;

Fereday, Sian ;

Caldas, Carlos ;

DeFazio, Anna ;

Bowtell, David ;

Brenton, James D. .

JOURNAL OF PATHOLOGY, 2010, 221 (01) :49-56

[2] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[3] BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation-Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group [J].

Alsop, Kathryn ;

Fereday, Sian ;

Meldrum, Cliff ;

deFazio, Anna ;

Emmanuel, Catherine ;

George, Joshy ;

Dobrovic, Alexander ;

Birrer, Michael J. ;

Webb, Penelope M. ;

Stewart, Colin ;

Friedlander, Michael ;

Fox, Stephen ;

Bowtell, David ;

Mitchell, Gillian .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (21) :2654-2663

[4] Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas [J].

Anglesio, Michael S. ;

Kommoss, Stefan ;

Tolcher, Mary C. ;

Clarke, Blaise ;

Galletta, Laura ;

Porter, Henry ;

Damaraju, Sambasivarao ;

Fereday, Sian ;

Winterhoff, Boris J. ;

Kalloger, Steve E. ;

Senz, Janine ;

Yang, Winnie ;

Steed, Helen ;

Allo, Ghassan ;

Ferguson, Sarah ;

Shaw, Patricia ;

Teoman, Attila ;

Garcia, Joaquin J. ;

Schoolmeester, John K. ;

Bakkum-Gamez, Jamie ;

Tinker, Anna V. ;

Bowtell, David D. ;

Huntsman, David G. ;

Gilks, C. Blake ;

McAlpine, Jessica N. .

JOURNAL OF PATHOLOGY, 2013, 229 (01) :111-120

[5] IL6-STAT3-HIF Signaling and Therapeutic Response to the Angiogenesis Inhibitor Sunitinib in Ovarian Clear Cell Cancer [J].

Anglesio, Michael S. ;

George, Joshy ;

Kulbe, Hagen ;

Friedlander, Michael ;

Rischin, Danny ;

Lemech, Charlotte ;

Power, Jeremy ;

Coward, Jermaine ;

Cowin, Prue A. ;

House, Colin M. ;

Chakravarty, Probir ;

Gorringe, Kylie L. ;

Campbell, Ian G. ;

Okamoto, Aikou ;

Birrer, Michael J. ;

Huntsman, David G. ;

de Fazio, Anna ;

Kalloger, Steve E. ;

Balkwill, Frances ;

Gilks, C. Blake ;

Bowtell, David D. .

CLINICAL CANCER RESEARCH, 2011, 17 (08) :2538-2548

[6] Clear cell carcinoma of the ovary: A report from the first Ovarian Clear Cell Symposium, June 24th, 2010 [J].

Anglesio, Michael S. ;

Carey, Mark S. ;

Koebel, Martin ;

MacKay, Helen ;

Huntsman, David G. .

GYNECOLOGIC ONCOLOGY, 2011, 121 (02) :407-415

[7] Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling [J].

Bashashati, Ali ;

Ha, Gavin ;

Tone, Alicia ;

Ding, Jiarui ;

Prentice, Leah M. ;

Roth, Andrew ;

Rosner, Jamie ;

Shumansky, Karey ;

Kalloger, Steve ;

Senz, Janine ;

Yang, Winnie ;

McConechy, Melissa ;

Melnyk, Nataliya ;

Anglesio, Michael ;

Luk, Margaret T. Y. ;

Tse, Kane ;

Zeng, Thomas ;

Moore, Richard ;

Zhao, Yongjun ;

Marra, Marco A. ;

Gilks, Blake ;

Yip, Stephen ;

Huntsman, David G. ;

McAlpine, Jessica N. ;

Shah, Sohrab P. .

JOURNAL OF PATHOLOGY, 2013, 231 (01) :21-34

[8] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[9] The Changing View of High-Grade Serous Ovarian Cancer [J].

Berns, Els M. J. J. ;

Bowtell, David D. .

CANCER RESEARCH, 2012, 72 (11) :2701-2704

[10] Mutation of the PIK3CA gene in ovarian and breast cancer [J].

Campbell, IG ;

Russell, SE ;

Choong, DYH ;

Montgomery, KG ;

Ciavarella, ML ;

Hooi, CSF ;

Cristiano, BE ;

Pearson, RB ;

Phillips, WA .

CANCER RESEARCH, 2004, 64 (21) :7678-7681

← 1 2 3 4 5 6 →