Grant Number:	1R21CA222867-01A1 Interpret this number
Primary Investigator:	Goode, Ellen
Organization:	Mayo Clinic Rochester
Project Title:	Epidemiology and Genomics of Ovarian Clear Cell Carcinoma
Fiscal Year:	2018

Epithelial ovarian cancer histotypes are thought to have numerous distinct inherited risk factors, somatic features, and clinical outcomes. Ovarian clear cell carcinoma (OCCC) is one of its rarer histotypes, representing approximately seven percent of diagnoses. For women presenting at advanced stage, it is highly lethal; the tumor tends to resist standard platinum-based chemotherapeutics. The more common histotypes, high-grade serous and endometrioid epithelial ovarian cancer, have been extensively studied including genomic characterization by large-scale efforts such as The Cancer Genome Atlas. Small-scale tumor profiling studies in OCCC suggest that it is distinct from these histotypes and that molecular subtypes of OCCC are likely to exist. Therefore, as the majority of findings from The Cancer Genome Atlas project are not expected to be applicable to OCCC, improving our understanding of the biology of OCCC with the goal of identifying genomic features which may lead to targeted OCCC therapeutics is of highest priority. We propose an exploratory study of OCCC patients from six studies, including targeting DNA sequencing, methylation profiling, and combined transcriptomic and proteomic expression analyses. We will identify which features most strongly associate with the baseline clinical features of OCCC patients, such as age at diagnosis, tumor grade, and stage, and with clinical outcomes, such as overall survival time and time to disease recurrence. To accomplish our aims, we will establish a collaborative epidemiologic network including investigators of studies representing the largest cohorts of OCCC cases with associated fresh frozen tumor specimens and clinical annotation. Based on the results obtained, we will conduct targeted follow-up in an independent collection of nearly 1,000 OCCC patients. As the majority of studied patients were enrolled into case-control studies which included germline genotyping and epidemiologic risk factor questionnaires, the wealth of knowledge to be gained is extensive. This will enable substantial progress towards the development of targeting therapeutics against this rare, frequently chemo-resistant cancer and will readily foster additional etiologic, epidemiologic, and clinical OCCC research.




Molecular Subclasses of Clear Cell Ovarian Carcinoma and Their Impact on Disease Behavior and Outcomes.
Authors: Bolton K.L. , Chen D. , Corona de la Fuente R. , Fu Z. , Murali R. , Köbel M. , Tazi Y. , Cunningham J.M. , Chan I.C.C. , Wiley B.J. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2022-11-14; 28(22), p. 4947-4956.
PMID: 35816189
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DNA Methylation Profiles of Ovarian Clear Cell Carcinoma.
Authors: Cunningham J.M. , Winham S.J. , Wang C. , Weiglt B. , Fu Z. , Armasu S.M. , McCauley B.M. , Brand A.H. , Chiew Y.E. , Elishaev E. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2022 Jan; 31(1), p. 132-141.
EPub date: 2021-10-25.
PMID: 34697060
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Frequent POLE-driven hypermutation in ovarian endometrioid cancer revealed by mutational signatures in RNA sequencing.
Authors: Davila J.I. , Chanana P. , Sarangi V. , Fogarty Z.C. , Weroha S.J. , Guo R. , Goode E.L. , Huang Y. , Wang C. .
Source: BMC medical genomics, 2021-06-22; 14(1), p. 165.
EPub date: 2021-06-22.
PMID: 34158040
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