Clinically Relevant Germline Mutations in a Cohort of Young Women with Breast Cancer: A Comprehensive Analysis of Hereditary-Cancer Genes from Whole-Exome Sequencing

Liliana Gomez-Flores-Ramos; Micheal Dean; Kristine Jones; Mingyi Wang; Cynthia Villarreal-Garza; Rosa María Álvarez-Gómez; Talia Wegman-Ostrosky; Nancy Reynoso-Noverón; Verónica Fragoso-Ontiveros; Luisa Sánchez-Zamorano; Miguel Trujillo-Martínez; Lizbeth Grimaldo; Patricia Gallegos-Arreola; Patricia Ostrosky-Wegman; Alejandro Mohar-Betancourt

doi:10.20944/preprints202008.0718.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 30 August 2020 / Approved: 31 August 2020 / Online: 31 August 2020 (09:46:26 CEST)

Young women with breast cancer represent 15% of cancer cases in Latin America. Genomic studies have found that early-onset breast-cancer cases exhibit a higher genetic susceptibility and a specific genomic signature as compared to their older counterparts. The aim of this study was to describe clinically relevant germline mutations in a cohort of young women with breast cancer. To achieve this, we analyzed hereditary-cancer genes from whole-exome sequencing data in 108 unrelated women with an extreme phenotype of breast cancer (≤40 years of age), diagnosed and treated at the National Cancer Institute of Mexico; 11% of the patients carried a pathogenic variant. BRCA2 comprised 46% of the mutations, followed by BRCA1 with 23%; PALB2 with 15%; and TP53 and RAD51C with 8 % each. This article describes a novel pathogenic mutation in RAD51C c.519dupT. The median age at diagnosis was 35 years overall; however, it was six years younger in patients with mutations. Age at diagnosis (OR=0.82, CI 95% 0.71-0.94; P= 0.008) and first-degree family history of cancer (OR=8.26, CI95% 1.35-50; P= 0.022) were the only epidemiological variables associated with mutational status. We found no differences in disease-free survival (p=0.403) or overall survival (p=0.735) among mutational status subgroups.

early-onset breast cancer; hereditary cancer; whole-exome sequencing; young women

Biology and Life Sciences, Biochemistry and Molecular Biology

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Clinically Relevant Germline Mutations in a Cohort of Young Women with Breast Cancer: A Comprehensive Analysis of Hereditary-Cancer Genes from Whole-Exome Sequencing

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