A novel de novo BRCA2 mutation of paternal origin identified in a Spanish woman with early onset bilateral breast cancer

Abstract

Germ line mutations in either of the two major breast cancer predisposition genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast/ovarian cancer. Identification of breast cancer patients carrying mutations in any of these genes is primarily based on a positive family history of breast/ovarian cancer or early onset of the disease. In the course of mutation screening of the BRCA1 and BRCA2 genes in a hospital based series of patients with risk factors for hereditary breast/ovarian cancer, we identified a novel germ line mutation in the BRCA2 gene (c.51dupA) in a patient with early onset bilateral breast cancer and no family history of the disease. None of her parents carried the mutation, and paternity was confirmed. Subsequent molecular analysis demonstrated that the mutation was a novel de novo germ line mutation located in the paternal allele of the BRCA2 gene.

Prevalence of BRCA1/2 mutations in sporadic breast/ovarian cancer patients and identification of a novel de novo BRCA1 mutation in a patient diagnosed with late onset breast and ovarian cancer: implications for genetic testing

“…Our data suggest a de novo event in a testicular germ cell, although a zygotic origin cannot be excluded. This is in agreement with previous findings in de novo mutations in BRCA1 and BRCA2, in which the paternal origin could be ascertained [8,12]. Of note, the age of the patients' father was only 29 years at the time of birth of his [39] c See ref [40] daughter.…”

“…To the best of our knowledge, to date only two de novo mutations in BRCA1 are reported [6,7] and five in BRCA2 [8][9][10][11][12]. All these mutations were identified in patients with tumors occurring before the age of 40. In this study, we present our data on the prevalence of BRCA1&2 mutations in 193 sporadic Belgian breast and/or ovarian cancer patients.…”

A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer

“…To date, just seven cases of de novo BRCA mutations have been reported in the literature, only two in the BRCA1 gene and five in BRCA2 [37-43] (Table 1). Concerning de novo mutations in BRCA1 , Tesoriero et al [38] report a woman with early-onset breast cancer with two germline protein-truncating mutations: BRCA1 c.3769_3770delGA and BRCA2 c.5946delT.…”

Breast and ovarian cancer predisposition due to de novo BRCA1 and BRCA2 mutations

“…However, in this study, only one out of four cases had a negative family history (case 2). The presence of a breast cancer family history has also been described in 5 of the 11 cases of de novo BRCA1/2 mutations reported in the literature [5][6][7][8][9][10][11][12][13][14][15] (Table 1). Breast cancer family history for de novo BRCA1/2 mutation carriers can have several origins: the high frequency of breast cancer in the general population; the strong impact of family history in the inclusion criteria for BRCA1/2 genetic testing, resulting in a bias for family cancer cases; and finally, genetic heterogeneity in breast cancer.…”

“…[1][2][3] More than 3000 distinct genetic variants have been reported in these genes (BRCA1 and BRCA2 Universal Mutation Databases 4 ). Despite the large number of mutation carriers identified by means of the large number of genetic tests conducted worldwide, only six BRCA1 and five BRCA2 de novo mutations have been reported [5][6][7][8][9][10][11][12][13][14][15] (Table 1). This small number is surprising, as the de novo mutation rate can be as high as 11-25% in APC, 74% in NF1 and up to 90% in RB1.…”