Haplotype analyses of the c.1027C>T and c.2167_2168delAT recurrent truncating mutations in the breast cancer-predisposing gene PALB2.
Breast Cancer Res Treat
; 160(1): 121-129, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27624329
ABSTRACT
PURPOSE:
Breast cancer-predisposing mutations PALB2 c.1027C>T (p.Gln343*) and PALB2 c.2167_2168delAT have each been observed multiple times in breast cancer families of Italian ancestry. More recently, the c2167_2168delAT mutation was identified in unrelated breast cancer cases of various ancestries. For each mutation, we investigated whether the origin was multiple mutational events (a "hot-spot") or a single event (a founder allele).METHODS:
We genotyped and reconstructed haplotypes for 36 participants of Italian, Italian-American, Hispanic, and Nigerian ancestries, using seven short tandem repeat (STR) markers that covered 3 Megabases within and flanking PALB2 on chromosome 16.RESULTS:
For PALB2 c.1027C>T, a shared haplotype with a minimum size of 150 kb was shared by all 19 carriers investigated, all of Italian ancestry. This result suggests that this allele arose as a single event in a shared ancestor. For PALB2 c.2167_2168delAT, all 12 carriers from American-Italian and Italian families shared a 1-Mb haplotype, the 3 Hispanic carriers shared a different haplotype of size 2 Mb, and the Nigerian carrier had different alleles at all 7 STR markers. These results suggest that PALB2 c.2167_2168delAT arose multiple times, but that within each population, PALB2 c.2167_2168delAT likely represents a single mutational event.CONCLUSION:
We identified two PALB2 mutations that are founder alleles in Italian families, one of which is, independently, also a founder mutation in American-Hispanic breast cancers.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Haplótipos
/
Neoplasias da Mama
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Predisposição Genética para Doença
/
Alelos
/
Proteína do Grupo de Complementação N da Anemia de Fanconi
/
Mutação
Limite:
Female
/
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Breast Cancer Res Treat
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Itália