Non- BRCA1/2 Variants Detected in a High-Risk Chilean Cohort With a History of Breast and/or Ovarian Cancer

Abstract

Methods: Data were retrospectively collected from the registry of the High-Risk Breast and Ovarian Cancer Program at Clínica Las Condes, Santiago, Chile. Data captured included index case diagnosis, ancestry, family history, and genetic test results.

Results: Three hundred fifteen individuals underwent genetic testing during the study period. The frequency of germline pathogenic and likely pathogenic variants in a breast or ovarian cancer predisposition gene was 20.3%. Of those patients who underwent testing with a panel of both high- and moderate-penetrance genes, 10.5% were found to have pathogenic or likely pathogenic variants in non-BRCA1/2 genes.

Conclusion: Testing for non-BRCA1 and -2 mutations may be clinically relevant for individuals who are suspected to have a hereditary breast or ovarian cancer syndrome in Chile. Comprehensive genetic testing of individuals who are at high risk is necessary to further characterize the genetic susceptibility to cancer in Chile.

FIG 1

Families with a likely pathogenic (LP) variant in RAD51C and an LP variant in ATM (all ages are ages provided at the time of first contact with index case). (A) Index case, carrier of LP variant in RAD51C c.404G>A. No family testing has been performed to date. (B) Index case, carrier of both LP variant in RAD51C c.404G>A and LP variant in ATM c.6154G>A. The daughter is also a carrier of both LP variants. Br, breast cancer; Ov, ovarian cancer.

FIG 2

Family with a pathogenic (P) variant in CDH1 (all ages are ages provided at the time of first contact with index case). Index case, carrier of P variant in CDH1 c.1565+2dupT. Mother, maternal half-brother, and monozygotic twin of index case are unaffected carriers. Br, breast cancer.

FIG 3

Families with pathogenic (P) variants in CHEK2 (all ages are ages provided at the time of first contact with index case). (A) Index case, carrier of P variant in CHEK2 c.1100delC. No family testing has been performed to date. (B) Index case, carrier of P variant in CHEK2 c.1344delT. No family testing has been performed to date. (C) Index case, carrier of P variant in CHEK2 c.1283C>T. Paternal uncle, carrier of P variant in BRCA2 c.5946delT. Index case tested negative for mutations in BRCA1 and BRCA2. Br, breast cancer; CRC, colorectal cancer; Pr, prostate cancer.

FIG 4

Families with pathogenic (P) variants in PALB2 (all ages are ages provided at the time of first contact with index case). (A) Index case, carrier of P variant in PALB2 c.860dupT. No family testing has been performed. (B) Index case, carrier of P variant in PALB2 c.3256C>T. Sister is a carrier. (C) Index case, carrier of P variant in PALB2 c.2964delA. No family testing has been performed to date. (D) Index case, carrier of both a P variant in PALB2 c.2218C>T and P variant in BRCA1 c.3817C>T. Br, breast cancer; Ov, ovarian cancer.

FIG 5

Family with a P variant in RAD51D (all ages are ages provided at the time of first contact with index case). Index case, carrier of P variant in RAD51D c.216C>A. No family testing has been performed to date. Br, breast cancer; Ov, ovarian cancer; Pr, prostate cancer.