Integrated Molecular Characterization of Uterine Carcinosarcoma

Robertson, Gordon; Kucherlapati, Raju; Akbani, Rehan; Ally, Adrian; Auman, J. Todd; Balasundaram, Miruna; Balu, Saianand; Baylin, Stephen B.; Beroukhim, Rameen; Bodenheimer, Tom; Bogomolniy, Faina; Boice, Lori; Bootwalla, Moiz S.; Bowen, Jay; Bowlby, Reanne; Broaddus, Russell R.; Brooks, Denise; Carlsen, Rebecca; Cherniack, Andrew D.; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cibulskis, Kristian; Cline, Melissa; Dao, Fanny; David, Mutch; Demchok, John A.; Dhalla, Noreen; Dowdy, Sean C.; Felau, Ina; Ferguson, Martin L.; Frazer, Scott; Frick, Jessica; Gabriel, Stacey; Gastier‐Foster, Julie M.; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Gupta, Manaswi; Haussler, David; Hayes, D. Neil; Heiman, David I.; Hess, Julian M.; Hoadley, Katherine A.; Hoffmann, Robert; Holt, Robert A.; Hoyle, Alan P.; Hu, Xin; Huang, Mei; Hutter, Carolyn M.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kanchi, Rupa S.; Kandoth, Cyriac; Kasaian, Katayoon; Kerr, Sarah E.; Kim, Jaegil; Lai, Phillip H.; Laird, Peter W.; Lander, Eric S.; Lawrence, Michael S.; Lee, Darlene; Leraas, Kristen; Leshchiner, Ignaty; Levine, Douglas A.; Lichtenberg, Tara M.; Lin, Pei; Ling, Shiyun; Liu, Jia; Liu, Wenbin; Liu, Yuexin; Lolla, Laxmi; Lu, Yiling; Ma, Yussanne; Maglinte, Dennis T.; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Mills, Gordon B.; Moore, Richard A.; Mose, Lisle E.; Mungall, Andrew J.; Mungall, Karen; Murray, Bradley A.; Naresh, Rashi; Noble, Michael S.; Olvera, Narciso; Parker, Joel S.; Perou, Charles M.; Perou, Amy H.; Pihl, Todd; Radenbaugh, Amie; Ramirez, Nilsa C.; Rathmell, W. Kimryn; Roach, Jeffrey; Robertson, A. Gordon; Sadeghi, Sara; Saksena, Gordon; Salvesen, Helga B.; Schein, Jacqueline E.; Schumacher, Steven E.; Shen, Hui; Sheth, Margi; Shi, Yan; Shih, Juliann; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Sofia, Heidi J.; Soloway, Matthew G.; Soslow, Robert A.; Sougnez, Carrie; Stewart, Chip; Sun, Charlie; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Thiessen, Nina; Thorne, Leigh B.; Tse, Kane; Tseng, Jill; Berg, David J. Van Den; Veluvolu, Umadevi; Verhaak, Roel G.W.; Voet, Doug; Bismarck, Amanda von; Walter, Vonn; Wan, Yunhu; Wang, Zhining; Wang, Chen; Weinstein, John N.; Weisenberger, Daniel J.; Wilkerson, Matthew D.; Winterhoff, Boris; Wise, Lisa; Wong, Tina; Wu, Ye; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan; Zhang, Hailei; Zhang, Wei; Zhu, Jingchun; Zmuda, Erik; Zuna, Rosemary E.

doi:10.1016/j.ccell.2017.02.010

Cited by 342 publications

(412 citation statements)

References 40 publications

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“…The original TCGA study excluded clear cell carcinomas and carcinosarcomas. These represent only about 5% of endometrial cancer cases each but are responsible for a disproportionate number of deaths because of their aggressive biology . For example, uterine carcinosarcoma accounts for 16% of all deaths caused by a uterine malignancy …”

Section: Prognostic Factorsmentioning

confidence: 99%

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Current recommendations and recent progress in endometrial cancer

Brooks

Fleming

Lastra

et al. 2019

CA A Cancer J Clinicians

441

372

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Endometrial cancer is the most common gynecologic cancer in the United States, and its incidence is rising. Although there have been significant recent advances in our understanding of endometrial cancer biology, many aspects of treatment remain mired in controversy, including the role of surgical lymph node assessment and the selection of patients for adjuvant radiation or chemotherapy. For the subset of women with microsatellite‐instable, metastatic disease, anti– programmed cell death protein 1 immunotherapy (pembrolizumab) is now approved by the US Food and Drug Administration, and numerous trials are attempting to build on this early success.

show abstract

Section: Prognostic Factorsmentioning

confidence: 99%

“…In 2017, TCGA published a molecular characterization of 57 uterine carcinosarcoma cases using the same integrated technique described for the characterization of endometrial carcinoma in 2013 . Two of 57 cases (4%) were MSI‐H.…”

Section: Prognostic Factorsmentioning

confidence: 99%

Current recommendations and recent progress in endometrial cancer

Brooks

Fleming

Lastra

et al. 2019

CA A Cancer J Clinicians

441

372

View full text Add to dashboard Cite

show abstract

“…At the genomic level, malignancies appear to be divided into two broad categories reflecting divergent oncogenic processes: copy number‐driven and mutation‐driven . Malignancies in the PanCancer12 analysis with high levels of somatic copy number alterations were associated with early TP53 mutations, reflecting the importance of TP53 in regulating genomic stability, and included ovarian carcinoma, squamous cell carcinoma, breast invasive ductal carcinoma, uterine serous carcinoma, uterine carcinosarcoma, and pleomorphic adult sarcomas . Mutation‐driven malignancies included clear cell renal cell carcinoma, glioblastoma, acute myeloid leukaemia, colorectal adenocarcinoma, and uterine non‐serous carcinomas.…”

Section: Major Findings From the Pancancer Analysis Projectmentioning

confidence: 99%

“…in uterine carcinosarcoma) or variant morphology (e.g. squamous or neuroendocrine differentiation in urothelial bladder carcinoma) . These facets are of undoubted importance, both for quality control of the analysed data, and to provide morphological correlates to molecular findings that might assist in translating molecular findings to clinical diagnostics.…”

Section: Limitations Of Tcga and Pancancer Analysis Projectsmentioning

confidence: 99%

PanCancer insights from The Cancer Genome Atlas: the pathologist's perspective

Cooper

Demicco

Saltz

et al. 2018

The Journal of Pathology

175

148

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The Cancer Genome Atlas (TCGA) represents one of several international consortia dedicated to performing comprehensive genomic and epigenomic analyses of selected tumour types to advance our understanding of disease and provide an open-access resource for worldwide cancer research. Thirty-three tumour types (selected by histology or tissue of origin, to include both common and rare diseases), comprising >11 000 specimens, were subjected to DNA sequencing, copy number and methylation analysis, and transcriptomic, proteomic and histological evaluation. Each cancer type was analysed individually to identify tissue-specific alterations, and make correlations across different molecular platforms. The final dataset was then normalized and combined for the PanCancer Initiative, which seeks to identify commonalities across different cancer types or cells of origin/lineage, or within anatomically or morphologically related groups. An important resource generated along with the rich molecular studies is an extensive digital pathology slide archive, composed of frozen section tissue directly related to the tissues analysed as part of TCGA, and representative formalin-fixed paraffin-embedded, haematoxylin and eosin (H&E)-stained diagnostic slides. These H&E image resources have primarily been used to verify diagnoses and histological subtypes with some limited extraction of standard pathological variables such as mitotic activity, grade, and lymphocytic infiltrates. Largely overlooked is the richness of these scanned images for more sophisticated feature extraction approaches coupled with machine learning, and ultimately correlation with molecular features and clinical endpoints. Here, we document initial attempts to exploit TCGA imaging archives, and describe some of the tools, and the rapidly evolving image analysis/feature extraction landscape. Our hope is to inform, and ultimately inspire and challenge, the pathology and cancer research communities to exploit these imaging resources so that the full potential of this integral platform of TCGA can be used to complement and enhance the insightful integrated analyses from the genomic and epigenomic platforms.

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“…In general, they are treated in a way similar to high-grade serous endometrial or ovarian malignancies, but its molecular landscape was far from being known. A paper published in Cancer Cell by the Cancer Genome Atlas Research Network reveals the most common molecular alterations harboured by them 3. In a very comprehensive analysis, including genomic, epigenomic, transcriptomic and proteomic characterisations of a series of 57 uterine carcinosarcomas, the authors show extensive copy number alterations as well as a high frequency of mutations.…”

Section: A Comprehensive Molecular Characterisation Of Uterine Carcinmentioning

confidence: 99%

In the literature: April 2017

Cervantes

2017

ESMO Open

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Integrated Molecular Characterization of Uterine Carcinosarcoma

Cited by 342 publications

References 40 publications

Current recommendations and recent progress in endometrial cancer

Current recommendations and recent progress in endometrial cancer

PanCancer insights from The Cancer Genome Atlas: the pathologist's perspective

In the literature: April 2017

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