Novel germline PALB2 truncating mutations in African American breast cancer patients

被引:32
作者
Zheng, Yonglan [1 ]
Zhang, Jing [1 ]
Niu, Qun [1 ]
Huo, Dezheng [2 ]
Olopade, Olufunmilayo I. [1 ]
机构
[1] Univ Chicago, Dept Med, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
breast cancer; PALB2; mutation; African American; sequencing; FANCONI-ANEMIA; PANCREATIC-CANCER; BRCA2-INTERACTING PROTEIN; SUSCEPTIBILITY GENE; FAMILIES; SUBSTITUTIONS; DATABASE; BRCA2; WOMEN; RISK;
D O I
10.1002/cncr.26388
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: 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. METHODS: 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. RESULTS: After direct sequencing of all the coding exons, exon/ intron boundaries, and 50 and 30 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. CONCLUSIONS: 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. Cancer 2012; 118: 1362-70. (C) 2011 American Cancer Society.
引用
收藏
页码:1362 / 1370
页数:9
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