Department of Genetics, University of Pretoria, Pretoria 0001, South Africa.
Fam Cancer. 2009;8(4):347-53. doi: 10.1007/s10689-009-9241-0. Epub 2009 Mar 31.
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.
PALB2（BRCA2 的伴侣和定位蛋白）是一个新发现的乳腺癌易感基因，其突变使乳腺癌风险增加一倍，具有中等到低外显率。最近在不同人群中的研究报告称，该基因中的有害突变约占家族性或早发性乳腺癌病例的 1%。本研究旨在确定 PALB2 突变是否参与了一组未经家族乳腺癌史选择的 48 名南非年轻（29-45 岁）乳腺癌患者。分析了 PALB2 的完整编码区和内含子-外显子边界。在一名患者中发现了一种新的截断突变 c.697delG (V233fs)。另一名患者中发现的错义变异（E211G）似乎与疾病分离，但使用 SIFT、PolyPhen 和 A-GVGD 进行的计算机分析表明该变异是非致病性的。此外，还检测到另外四个错义、一个同义和三个内含子变异，所有这些变异似乎都是多态性的。这是第二项分析 PALB2 在未经家族史选择的早发性乳腺癌患者中的作用的研究。第一项针对中国人群的研究确定 PALB2 导致了 1.3%的早发性乳腺癌病例。我们的研究报告称，PALB2 中的有害突变约占南非早发性乳腺癌的 2%（1/48）。
