Frequency of Mutations in Multigene Panel Testing of 324 Ovarian and/or Endometrial Cancer Patients

November 2017 Vol 8, No 11
Will McFadden, PhD
Color Genomics, Burlingame, CA
Lilian Servais, MS, LCGC
Color Genomics, Burlingame, CA
Jeroen van den Akker, PhD
Color Genomics, Burlingame, CA
Anjali Zimmer, PhD
Color Genomics, Burlingame, CA

Background: Endometrial and ovarian cancers are the sixth and seventh most common cancers in women worldwide.1 Inherited germline mutations in genes such as BRCA1 and BRCA2 have been identified in 6% to 24% of women with gynecologic cancers.2-4 The identification of mutations in gynecologic cancer susceptibility genes in healthy women may allow more personalized cancer risk management, surveillance, chemopreventive approaches, and/or prophylactic surgeries. For women already diagnosed with a gynecologic cancer, the identification of mutations may provide potential targets for biologic agents and guide treatment decisions.

Objectives: Here we describe the demographics and characteristics of 324 individuals with a self-reported diagnosis of ovarian and/or endometrial cancer who received a 30-gene panel genetic test for hereditary cancer risk.

Methods: These 324 patients were referred for hereditary cancer testing by their healthcare provider. All patient demographic information was collected via a self-reported online health history questionnaire.

Results: In this cohort, the median reported age at cancer diagnosis was 53 and 54 years for ovarian and endometrial cancers, respectively. Overall, a total of 49 individuals were found to carry a single pathogenic or likely pathogenic mutation in 1 of the 30 genes tested, and 4 individuals were found to carry 2 concurrent pathogenic mutations. Notably, 24 of the 57 mutations identified were reported in the BRCA1 and BRCA2 genes, yielding an overall BRCA1 and BRCA2 mutation rate of 7.4%. In total, a pathogenic mutation was identified in 12 of the 30 genes, including several genes with known ovarian/endometrial cancer risks (BRCA1, BRCA2, BRIP1, MLH1, MSH2, PALB2, RAD51C, and RAD51D), as well as some genes with less established gynecologic cancer risk (ATM and CHEK2). In addition, 3 patients—2 ovarian cancer patients and 1 endometrial cancer patient—were found to carry a single pathogenic mutation in MUTYH, and 3 ovarian cancer patients and 1 endometrial cancer patient were found to carry the APC c.3920T>A (I1307K) mutation. Because neither of these genes have previously been associated with increased ovarian/endometrial cancer risk, these mutations are considered incidental findings and are unlikely to be the cause of the patient’s disease.

Conclusions: In summary, the overall mutation carrier rate in this cohort for known breast/ovarian cancer risk genes was 10.8% (35/324). Taken together, these data support the recommendation that all patients with gynecologic cancers should undergo broad germline testing for hereditary cancer risk.

Disclosure: This work was sponsored by Color Genomics.


  1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.1. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013. Accessed January 16, 2015.
  2. Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108:18032-18037.
  3. Susswein LR, Marshall ML, Nusbaum R, et al. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med. 2015;18:823-832.
  4. LaDuca H, Stuenkel AJ, Dolinsky JS, et al. Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med. 2014;16:830-837.
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