RESUMO
PALB2 (partner and localizer of BRCA2) is a recently identified breast cancer susceptibility gene, in which mutations confer doubling of breast cancer risk with moderate to low penetrance. Recent studies in various populations report that deleterious mutations in this gene account for approximately 1% of familial or early-onset breast cancer cases. This study aimed to determine the involvement of PALB2 mutations in a cohort of 48 young (29-45 years) South African breast cancer patients unselected for family history of breast cancer. The complete coding region and intron-exon boundaries of PALB2 were analyzed. A novel truncating mutation, c.697delG (V233fs) was identified in one patient. A missense variant (E211G), identified in another patient, appears to be segregating with the disease, but in silico analysis using SIFT, PolyPhen and A-GVGD, indicates that this variant is nonpathogenic. In addition, four other missense, one synonymous and three intronic variants were detected, all of which appear polymorphic. This represents the second study to analyze the role of PALB2 in early-onset breast cancer patients unselected for family history. The first study, of a Chinese population, established that PALB2 was responsible for 1.3% of early-onset breast cancer cases. Our study reports that deleterious mutations in PALB2 account for approximately 2% (1/48) of South African early-onset breast cancer.
