PALB2 mutations in familial breast and pancreatic cancer
PALB2 mutations in familial breast and pancreatic cancer
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DOI：
10.1007/s10689-011-9426-1
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发表时间：
2011-06-01
期刊：
影响因子：
2.2
通讯作者：
Tung, Nadine
中科院分区：
文献类型：
--
作者：
Hofstatter, Erin W.;Domchek, Susan M.;Tung, Nadine
PALB2 （BRCA2的伴侣和定位器）在DNA修复中与BRCA2结合并共定位。在大约1-2%的家族性乳腺癌和3-4%的家族性胰腺癌病例中发现了PALB2的种系突变。本研究的目的是评估PALB2突变在没有BRCA1/2突变且有胰腺癌个人或家族史的乳腺癌女性中的患病率。对94例个人或家族有胰腺癌病史的非brca1 /2乳腺癌患者进行PALB2突变分析。发现两个截断PALB2突变，c.3549C > CA和c.2962C > CT，导致突变发生率为2.1%。发现携带c.3549C > CA PALB2突变的先证者的母亲同时被诊断患有乳腺癌和胰腺癌；该亲属随后被证实携带相同的突变。具有c.2962C > CT突变的先证者的父亲和父亲的阿姨被诊断患有胰腺癌；两名亲属都无法接受检测。还发现了两种新的PALB2错义变体，其中一种被认为是潜在有害的。与迄今为止研究的其他乳腺癌人群相比，专门选择具有胰腺癌家族史的非brca1 /2乳腺癌人群中PALB2突变的患病率似乎没有显著增加。需要进一步的评估来确定PALB2突变的患病率以及这种检测在乳腺癌和胰腺癌患者中的临床应用。
PALB2 (Partner And Localizer of BRCA2) binds to and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1-2% of familial breast cancer and 3-4% of familial pancreatic cancer cases. The goal of this study was to evaluate the prevalence of PALB2 mutations in women with breast cancer without BRCA1/2 mutations who also had a personal or family history of pancreatic cancer. PALB2 mutation analysis was performed in 94 non-BRCA1/2 breast cancer patients with a personal or family history of pancreatic cancer. Two truncating PALB2 mutations, c.3549C > CA and c.2962C > CT, were identified resulting in a mutation prevalence of 2.1%. The proband found to carry the c.3549C > CA PALB2 mutation had a mother diagnosed with both breast and pancreatic cancer; this relative was subsequently confirmed to carry the identical mutation. The proband with the c.2962C > CT mutation had a father and paternal aunt diagnosed with pancreatic cancer; neither relative was available for testing. Two novel PALB2 missense variants were also found, one of which was deemed potentially deleterious. The prevalence rate of PALB2 mutations in a non-BRCA1/2 breast cancer population specifically selected for a family history of pancreatic cancer does not appear to be significantly increased compared to that observed in other breast cancer populations studied thus far. Further evaluation is needed to determine the prevalence of PALB2 mutations and the clinical utility of such testing in those individuals affected with both breast and pancreatic cancers.