Integrated Genomic Analyses of Ovarian Carcinoma

  title={Integrated Genomic Analyses of Ovarian Carcinoma},
  author={Deborah Bell and Andrew Berchuck and Michael J. Birrer and Jeremy Chien and Daniel W. Cramer and Fanny Dao and Rajiv Dhir and Philip John Disaia and Hani Gabra and Pat Glenn and Andrew K. Godwin and Jenny Gross and Lynn C. Hartmann and M Huang and David G. Huntsman and Mary V. Iacocca and Marcin Imieliński and Steve E Kalloger and Beth Y. Karlan and Douglas A. Levine and Gordon B. Mills and Carl D. Morrison and David G. Mutch and Narciso Olvera and Sandra Orsulic and K. Park and Nicholas J. Petrelli and Brenda Rabeno and Janet S. Rader and Branimir Sikic and Karen Smith-McCune and Anil K. Sood and David D. L. Bowtell and Robert J. Penny and Joseph R. Testa and K. Chang and Huyen Dinh and Jennifer Drummond and Gerald R. Fowler and Preethi H. Gunaratne and Alicia C. Hawes and Christie L. Kovar and Lora R. Lewis and Margaret B. Morgan and Irene Newsham and Jireh Santibanez and Jeffrey G. Reid and Lisa R. Trevi{\~n}o and Y. Wu and M. W. Wang and Donna M. Muzny and David A. Wheeler and Richard A. Gibbs and Gad Getz and Michael S. Lawrence and Kristian Cibulskis and Andrey Y. Sivachenko and Carrie Sougnez and Douglas Voet and Jane Wilkinson and Toby Bloom and Kristin G. Ardlie and Tim Fennell and Jennifer Baldwin and S. Gabriel and Eric S. Lander and Li Ding and Robert S. Fulton and Daniel C. Koboldt and Michael D. McLellan and Todd N. Wylie and Jason R. Walker and Michelle D. O'Laughlin and David J. Dooling and Lucinda Fulton and Rachel M. Abbott and Nathan D. Dees and Q. Zhang and Cyriac Kandoth and Michael C. Wendl and William S. Schierding and Dong Shen and Christopher C. Harris and Hayden R. Schmidt and Joelle Kalicki and Kim D. Delehaunty and Catrina C. Fronick and Ryan T. Demeter and Lisa L. Cook and John W. Wallis and L I Lin and Vincent J. Magrini and Jennifer Hodges and James M. Eldred and S. M. Smith and Craig S. Pohl and Fabio Vandin and Benjamin J. Raphael and George M. Weinstock and Elaine R. Mardis and Richard K. Wilson and Matthew L Meyerson and Wendy Winckler and Roel G. W. Verhaak and Suzie Carter and Craig H. Mermel and Gordon Saksena and Hoang Nguyen and Roberto Onofrio and Diana D. Hubbard and Sumit Gupta and Andrew Crenshaw and Alex H. Ramos and Lynda Chin and Alexei Protopopov and Juinhua Zhang and T. Kim and Ilana Perna and Y. Xiao and Hailei Zhang and Gang Ren and Narayanan Sathiamoorthy and Richard W. Park and Eunjung Alice Lee and Peter J. Park and Raju Kucherlapati and Devin M Absher and Lindsay L. Waite and Gavin Sherlock and James D. Brooks and Jun Li and Jin Xu and Richard M. Myers and Peter W. Laird and Leslie M. Cope and James Gordon Herman and Hui Shen and Daniel J. Weisenberger and Houtan Noushmehr and Fei Pan and Timothy J. Triche and Benjamin Paul Berman and David J. Van Den Berg and Jonathan D. Buckley and Stephen B. Baylin and Paul T. Spellman and Elizabeth Purdom and Pierre Neuvial and Henrik Bengtsson and Lakshmi R. Jakkula and Steffen Durinck and J Han and Shannon Dorton and Henry Marr and Y. Choi and Victoria E. H. Wang and Ninghai Wang and John Ngai and John G Conboy and Bahram Parvin and Heidi S. Feiler and Terence P. Speed and Joe W. Gray and Nicholas D. Socci and Yanke Liang and Barry S. Taylor and Nikolaus D. Schultz and Laetitia Borsu and Alex E. Lash and Cameron W. Brennan and Agnes Viale and Chris Sander and Marc Ladanyi and Katherine A. Hoadley and Shaowu Meng and Yingying Du and Yufeng Shi and Lulin Li and Y. J. Turman and Dan Zang and Erin Helms and Saianand Balu and X. Zhou and Jinhua Wu and Michael D. Topal and David Neil Hayes and Charles M. Perou and Jun Zhang and Chaowei Wu and Sk Shukla and Andrey Y. Sivachenko and Rui Jing and Yueh-Feng Liu and Michael S. Noble and Hannah Carter and D. Kim and Rachel Karchin and James E Korkola and Laura M. Heiser and Raymond J. Cho and Zhihao Hu and Ethan G. Cerami and Adam B. Olshen and Boris Reva and Yevgeniy Antipin and Ronglai Shen and Parminder Mankoo and Robert L. Sheridan and Giovanni Domenico Ciriello and William K. Chang and Joel A Bernanke and David Haussler and Christopher C. Benz and Joshua M. Stuart and Stephen Charles Benz and J. Zachary Sanborn and Charles J. Vaske and Jiangyu Zhu and Christopher Szeto and Gary K. Scott and Christina Yau and Matthew D. Wilkerson and N. Zhang and Rehan Akbani and Keith A. Baggerly and W. K. A. Yung and John N. Weinstein and Troy Shelton and Dirk Grimm and Martha Hatfield and Scott Morris and Peggy Yena and Paula S. Rhodes and Mark E. Sherman and Joseph D. Paulauskis and Sherri Z. Millis and Ari B. Kahn and John M. Greene and Robert Sfeir and Mark A. Jensen and James K. Chen and John H. Whitmore and Shelley Alonso and Jason Jordan and Anna L. Chu and Jinghui Zhang and Anna D Barker and Carolyn C. Compton and Greg Eley and Martin L Ferguson and Peter Fielding and Daniela S. Gerhard and Renate Myles and Carl F. Schaefer and Kenna R. Mills Shaw and Jimmie B. Vaught and Joseph Vockley and Peter J. Good and Mark Guyer and Bradley A Ozenberger and James Peterson and Elizabeth J. Thomson},
  pages={609 - 615}
A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in… 

Genomic/Epigenomic Alterations in Ovarian Carcinoma: Translational Insight into Clinical Practice

Gene mutations, copy number aberrations and DNA methylations provided promising biomarkers for the detection, diagnosis, prognosis, therapy response and targets of ovarian cancer, and underscore the necessity to translate these potential biomarkers into clinical practice.

Non-equivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations

The molecular differences between tumors associated with B RCA1 compared with BRCA2 mutations accords with emerging clinical and pathological data, and support a growing appreciation of the relationship between HGSC and BLBC.

Integrated genomic characterization of endometrial carcinoma

  • D. LevineGad Stacey B. Kristian Eric Andrey Carrie Mike Cyriac Getz Gabriel Cibulskis Lander Sivachenko Sougnez L H. Sofia
  • Biology, Medicine
  • 2013
The genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours, and these features are classified into four categories: POLE ultramutated, microsatellite instability hypermutated, copy- number low, and copy-number high.

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas

Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas, however, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCa-related patients likely to respond to PARP inhibitors.

Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes

This 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.

Comprehensive molecular portraits of human breast tumors

The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.

The clinical importance of BRCAness in a population-based cohort of Danish epithelial ovarian cancer

The BRCAness phenotype is present in almost one-fourth of epithelial ovarian carcinoma and holds important prognostic information, and was associated with improved overall survival in the high-grade serous carcinoma subgroup.

Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells

Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity, and improvements in the understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments.



Comprehensive genomic characterization defines human glioblastoma genes and core pathways

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.

Somatic mutations affect key pathways in lung adenocarcinoma

Somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B are found.

Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors.

BACKGROUND Inherited mutations in the BRCA1 gene may be responsible for almost half of inherited breast carcinomas. However, somatic (acquired) mutations in BRCA1 have not been reported, despite

Integrated Genome-Wide DNA Copy Number and Expression Analysis Identifies Distinct Mechanisms of Primary Chemoresistance in Ovarian Carcinomas

Two distinct mechanisms of primary treatment failure in serous ovarian cancer are identified, involving CCNE1 amplification and enhanced extracellular matrix deposition, andCCNE1 copy number is validated as a dominant marker of patient outcome in ovarian cancer.

The landscape of somatic copy-number alteration across human cancers

It is demonstrated that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival, and a large majority of SCNAs identified in individual cancer types are present in several cancer types.

ARID1A mutations in endometriosis-associated ovarian carcinomas.

These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas.

Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary

It is concluded that mutant TP53 is a driver mutation in the pathogenesis of HGPSC cancers because it is almost invariably present in HGPSCs, and is not of substantial prognostic or predictive significance.

p53 mutation is infrequent in clear cell carcinoma of the ovary.

Mutations in p53 appear to be much less frequent in clear cell carcinoma than in other histologic types of epithelial ovarian cancer, and it is suggested that p53 alterations may not play an important role in the development of clear cell cancer.

Prioritization of driver mutations in pancreatic cancer using cancer-specific high-throughput annotation of somatic mutations (CHASM)

Over 20,000 genes were recently sequenced in a series of 24 pancreatic cancers and CHASM identified putative driver mutations in three known pancreatic cancer driver genes (P53, SMAD4, CDKN2A), which point to potential "driver genes" in pancreaticcancer that should be prioritized for additional follow-up.