PALB2 sequence variants in young South African breast cancer patients

Abstract

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.

Association between rs120963, rs152451, rs249935, rs447529, rs8053188, and rs16940342 Polymorphisms in the <b><i>PALB2</i></b> Gene and Breast Cancer Susceptibility: A Meta-Analysis

“…Many studies previously reported that mutations in the PALB2 gene showed evidence of being correlated with a significantly increased risk of breast cancer [9,10,11,12], especially hereditary breast cancer [13,14]. Mutations in the PALB2 gene confer a doubled breast cancer risk with moderate-to-low penetrance [15]. Our previous meta-analysis also indicated that polymorphism in the PALB2 gene locus rs249954 was associated with breast cancer risk, and we already demonstrated that a heterozygous (CT) genotype in PALB2 gene locus rs249954 increases breast cancer susceptibility (table 8) [7].…”

PALB2 analysis in BRCA2-like families

“…In total, 77 PALB2 mutation-positive cases have been identified mainly in familial or early onset breast cancer cohorts from different populations [13,15,[18][19][20][21][22][23][24][25]. Of the 77 described PALB2 mutation cases, 52 are carrier of the 1592delT Finnish founder mutation, which could influence the currently known phenotype [19,24,26].…”

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

“…According to different ethnic reports [95][96][97][98][99][100] , about 1% of women with early-onset BCs negative for BRCA1/2 mutations carry a mutation in this gene.…”