High prevalence of BRCA1 founder mutations in Greek breast/ovarian families

Abstract

We have screened 473 breast/ovarian cancer patients with family history, aiming to define the prevalence and enrich the spectrum of BRCA1/2 pathogenic mutations occurring in the Greek population. An overall mutation prevalence of 32% was observed. Six BRCA1 recurrent/founder mutations dominate the observed spectrum (58.5% of all mutations found). These include three mutations in exon 20 and three large genomic deletions. Of the 44 different deleterious mutations found in both genes, 16 are novel and reported here for the first time. Correlation with available histopathology data showed that 80% of BRCA1 carriers presented a triple-negative breast cancer phenotype while 82% of BRCA2 carriers had oestrogen receptor positive tumours. This study provides a comprehensive view of the frequency, type and distribution of BRCA1/2 mutations in the Greek population as well as an insight of the screening strategy of choice for patients of Greek origin. We conclude that the Greek population has a diverse mutation spectrum influenced by strong founder effects.

Multicenter cross‑sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations

“…This finding is in line with a Korean study conducted across 36-centers (22.3%) (17). The mutation rate appears generally lower compared to Western countries (23~35.3%) (18)(19)(20)(21)(22), but higher compared to Peking or Shanghai regions (10.5~18.2%) (23)(24)(25). Lower prevalence of BRCA mutation is in line with comparisons of BC incidence with the Western countries.…”

Síndrome de cáncer hereditario de mama y ovario: aplicación clínica

“…Los cánceres de mama asociados a la mutación del gen BRCA1 son con frecuencia negativos para la presencia de receptores de estrógeno, progesterona, y la sobreexpresión de HER-2/Neu (triple negativo) (30)(31)(32)(33). El 90 % de los tumores debidos a mutaciones en BRCA1 son triple negativos por inmunohistoquímica (19); además, en pacientes con tumores TN, la probabilidad de estar ligados a mutaciones BRCA1 es mayor que en las clasificadas como NO triple negativo, con un RR = 5,65 (IC 95 %: 4,15-7,69) (34); sin embargo, se desconoce la proporción exacta de tumores triple negativos que poseen mutaciones en BRCA1 (20).…”

“…Por otro lado, aquellos fenotipos TN ligados a mutación BRCA1 han mostrado edades de aparición más temprana que otros no ligados a mutación (35). Los tumores debido a mutaciones en BRCA2, al contrario que los de BRCA1, son positivos para receptores de estrógeno y progesterona, asemejándose a los tumores de cánceres no hereditarios (20,29,30,33,36).…”

Improved DNA microarray detection sensitivity through immobilization of preformed in solution streptavidin/biotinylated oligonucleotide conjugates

“…These mutations present different levels of difficulty in achieving good discrimination between wild and mutant sequences, with single nucleotide polymorphisms (SNPs) presenting the highest challenge. In addition, the specific mutations were selected because they cover more than 50% of the hereditary breast/ovarian cancer cases with mutations in BRCA1 gene among individuals with ascertained hereditary predisposition to breast/ovarian cancer in the Greek population [38,39].…”

“…Furthermore, in order to gain more insight information about the surface topography and the composition of the biomolecular layers formed following each immobilization approach, the surfaces were characterized by Atomic Force Microscopy and Time of Flight-Secondary Ion Mass Spectrometry. Finally, the proposed immobilization approach was evaluated in comparison to immobilization approach A in terms of real sample analysis, through the development of a microarray for the detection of three most common and four less frequent mutations in Breast Cancer 1 (BRCA1) tumor suppressor gene among those individuals with ascertained hereditary predisposition to breast/ovarian cancer in the Greek population [38,39].…”