A germline mosaic BRCA1 exon deletion in a woman with bilateral basal‐like breast cancer

Low-level constitutional mosaicism of a de novoBRCA1 gene mutation

“…A few cases of de novo constitutional BRCA1 or BRCA2 have previously been described, but most were detected in a heterozygous form in constitutional DNA and were not mosaic ( Tesoriero et al , 1999 ; Robson et al , 2002 ; Hansen et al 2008 ; Edwards et al , 2009 ; Marshall et al , 2009 ; Garcia-Casado et al , 2011 ; Kwong et al , 2011 ; Zhang et al , 2011 ) or detected at a high frequency of >70% of cells ( Delon et al , 2013 ). The per cent of hereditary breast ovarian cancer cases that can be attributed to low-level constitutional mosaicism is not known at this time.…”

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.…”

“…28 To our knowledge, only one BRCA1 mosaic deletion has been previously described, which has been identified in a woman diagnosed with bilateral breast cancer. 10 Even if BRCA1/2 mosaic mutations may be rare, their detection is important as they result in predisposition to breast and ovarian cancer for the carrier patient and there is up to 50% risk of transmission to offspring. …”

Many Mosaic Mutations

“…Further investigation has revealed that up to one fifth of these apparently de novo cases are actually attributable to gonadal mosaicism, which in some cases has extended to include other tissues, but has not resulted in "full-blown" polyposis 4 . Mosaicism has in fact been reported for many cancer susceptibility genes 5,6 -most recently, for BRCA1 7 . Because the first case will always be sporadic, it is quite likely that these heritable mutations will remain unrecognized.…”