Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
Cancer. 2012 Mar 1;118(5):1362-70. doi: 10.1002/cncr.26388. Epub 2011 Aug 26.
It has been demonstrated that the partner and localizer of breast cancer 2 (PALB2) acts as a bridging molecule between the breast cancer 1 (BRCA1) and BRCA2 proteins and is responsible for facilitating BRCA2-mediated DNA repair. Truncating mutations in the PALB2 gene reportedly are enriched in patients with Fanconi anemia and breast cancer in various populations.
The authors evaluated the contribution of PALB2 germline mutations in 279 African American women with breast cancer, including 29 patients with a strong family history, 29 patients with a moderate family history, 75 patients with a weak family history, and 146 patients with nonfamilial or sporadic breast cancer.
After direct sequencing of all the coding exons, exon/intron boundaries, and 5' and 3' untranslated regions of PALB2, 3 novel, monoallelic, truncating mutations (1.08%; 3 in 279 patients) were identified (c.758dupT [exon 4], c.1479delC [exon 4], and c.3048delT [exon 10]) together with 50 sequence variants, 27 of which were novel. None of the truncating mutations were identified in a group of 262 controls from the same population.
PALB2 mutations were present in both familial and nonfamilial breast cancers among African Americans. Rare PALB2 mutations accounted for a small but substantial proportion of patients with breast cancer.
已经证实，乳腺癌 2 号（PALB2）的伴侣和定位蛋白作为乳腺癌 1 号（BRCA1）和 BRCA2 蛋白之间的桥接分子，负责促进 BRCA2 介导的 DNA 修复。在不同人群中，报道称 PALB2 基因中的截断突变在范可尼贫血和乳腺癌患者中富集。
作者评估了 PALB2 种系突变在 279 名非裔美国乳腺癌患者中的贡献，包括 29 名有强烈家族史的患者、29 名有中度家族史的患者、75 名有轻度家族史的患者和 146 名非家族性或散发性乳腺癌患者。
对 PALB2 的所有编码外显子、外显子/内含子边界以及 5'和 3'非翻译区进行直接测序后，鉴定出 3 种新的单等位基因截断突变（1.08%；279 例患者中有 3 例）（c.758dupT [exon 4]、c.1479delC [exon 4]和 c.3048delT [exon 10]），同时还鉴定出 50 种序列变异，其中 27 种是新的。在来自同一人群的 262 名对照者中，未发现任何截断突变。
PALB2 突变存在于非裔美国人的家族性和非家族性乳腺癌中。罕见的 PALB2 突变占乳腺癌患者的一小部分，但比例相当大。
