0000000000535266
AUTHOR
Ana Vega
Mutational analysis ofBRCA1andBRCA2in Mediterranean Spanish women with early-onset breast cancer: Identification of three novel pathogenic mutations
In Spain, the contribution of BRCA mutations to the population incidence of early-onset breast cancer was unknown. We carried out a mutational analysis of the BRCA1 and BRCA2 genes in 124 Spanish women diagnosed with breast cancer before the age 41 and who were not selected for a family history of this disease. The genetic study was performed by PCR-SSCP analysis and DNA sequencing. We identified 6 pathogenic BRCA mutations in 7 unrelated probands (5.6%; 95% CI=2.3% to 11.3%): 1 BRCA1 (c.2080delA) and 5 BRCA2 (p.Y3006X, p.Q1994X, c.9204_9217del14, c.9254_9258del5 and c.295+2T>C). Three out of 6 mutations were novel (BRCA2 p.Y3006X, c.9204_9217del14, and c.295+2T>C), and two further mutation…
Analysis ofBRCA1andBRCA2genes in Spanish breast/ovarian cancer patients: A high proportion of mutations unique to Spain and evidence of founder effects
We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ-line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site-specific female breast cancer families (15.4%). Of the families with male breast cancer cases, …
A Novel Loss-of-Function Mutation (N48K) in the PTEN Gene in a Spanish Patient with Cowden Disease
Cowden disease, also known as multiple hamartoma syndrome, is a rare disease inherited in an autosomal dominant pattern, which confers a high risk of developing breast and thyroid carcinomas. Mutations in PTEN, a tumor suppressor gene located on chromosome 10q23, have been identified in patients with Cowden disease. In this work, the direct sequencing of all coding regions of the PTEN gene led us to the identification of N48K, a new germline PTEN missense mutation, in a patient suffering from Cowden disease. The genetic analysis of 200 chromosomes from healthy individuals revealed that the variant was not common in our population. Moreover, by functional analysis we found that the ability o…