. 2016 Feb;140(2):221-5.

doi: 10.1016/j.ygyno.2015.12.017. Epub 2015 Dec 21.

Genetic characterization of early onset ovarian carcinoma

Sarah S Bernards¹, Barbara M Norquist², Maria I Harrell³, Kathy J Agnew⁴, Ming K Lee⁵, Tom Walsh⁶, Elizabeth M Swisher⁷

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: sarahb18@uw.edu.
² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: bnorquis@uw.edu.
³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: maribel@uw.edu.
⁴ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: kagnew@uw.edu.
⁵ Division of Medical Genetics, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: mlee@uw.edu.
⁶ Division of Medical Genetics, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: twalsh@uw.edu.
⁷ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA; Division of Medical Genetics, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: swishere@uw.edu.

PMID: 26718727
PMCID: PMC4869974
DOI: 10.1016/j.ygyno.2015.12.017

Genetic characterization of early onset ovarian carcinoma

Sarah S Bernards et al. Gynecol Oncol. 2016 Feb.

. 2016 Feb;140(2):221-5.

doi: 10.1016/j.ygyno.2015.12.017. Epub 2015 Dec 21.

Authors

Sarah S Bernards¹, Barbara M Norquist², Maria I Harrell³, Kathy J Agnew⁴, Ming K Lee⁵, Tom Walsh⁶, Elizabeth M Swisher⁷

Affiliations

¹ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: sarahb18@uw.edu.
² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: bnorquis@uw.edu.
³ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: maribel@uw.edu.
⁴ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: kagnew@uw.edu.
⁵ Division of Medical Genetics, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: mlee@uw.edu.
⁶ Division of Medical Genetics, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: twalsh@uw.edu.
⁷ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA; Division of Medical Genetics, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, WA 98195, USA. Electronic address: swishere@uw.edu.

PMID: 26718727
PMCID: PMC4869974
DOI: 10.1016/j.ygyno.2015.12.017

Abstract

Objective: Ovarian carcinoma (OC) is rare in young women and the fraction of early onset OC attributable to inherited mutations in known OC genes is uncertain. We sought to characterize the fraction of OC that is heritable in women diagnosed with ovarian, fallopian tube, or peritoneal carcinoma at forty years of age or younger.

Methods: We sequenced germline DNA from forty-seven women diagnosed with OC at age 40 or younger ascertained through a gynecologic oncology tissue bank or referred from outside providers using BROCA, a targeted capture and massively parallel sequencing platform that can detect all mutation classes. We evaluated 11 genes associated with ovarian carcinoma (BARD1, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, PALB2, PMS2, RAD51D, and RAD51C) and additional candidate genes in DNA repair (ATM, BAP1, CHEK2, MRE11A, NBN, PTEN, TP53). We counted only clearly damaging mutations.

Results: Damaging mutations in OC genes were identified in 13 of 47 (28%) subjects, of which 10 (77%) occurred in BRCA1 and one each occurred in BRCA2, MSH2, and RAD51D. Women with a strong family history were no more likely to have an OC gene mutation (8/17, 47%) than those without a strong family history (9/30, 30%, P=0.35). Additionally, damaging mutations in non-OC genes were identified, one in NBN and one in CHEK2.

Conclusions: A high proportion of young women with invasive OC have mutations in BRCA1, and a smaller fraction have mutations in other known OC genes. Family history was not associated with mutation status in these early onset cases.

Keywords: BRCA1; BRCA2; Carcinoma; Inherited; Ovarian; Young.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

**Fig. 1**
Pedigree of MSH2 mutation carrier diagnosed with OC at age 37 (arrow). Cancers and age of diagnosis are presented for relatives with Lynch-related cancers shaded in black. This family meets Amsterdam revised criteria for Lynch syndrome.

See this image and copyright information in PMC

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Genetic characterization of early onset ovarian carcinoma

Affiliations

Genetic characterization of early onset ovarian carcinoma

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous