PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo
PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo
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DOI：
10.1038/gim.2014.13
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发表时间：
2014-09-01
影响因子：
8.8
通讯作者：
Radice, Paolo
中科院分区：
文献类型：
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作者：
Catucci, Irene;Peterlongo, Paolo;Radice, Paolo
目的：PALB2(BRCA2的配对和定位基因)的单等位基因种系有害突变与乳腺癌风险相关，已在多个人群中发现，携带率接近1-2%。最初，这些突变被认为具有中等外显性，但现在越来越多的证据表明，它们与更高的风险相关。方法：在本研究中，我们对575名来自米兰的意大利乳腺癌家系的先证者的PALB2编码区进行了测序。结果：我们发现了12名携带者(2.1%)的有害突变，而在米兰收集的784名对照中没有发现任何突变。其中一个突变，c.1027C>；T(p.Gln343X)，在意大利北部的贝加莫省被发现是复发的，在该地区招募的6/113(5.3%)家族性乳腺癌病例和2/477(0.4%)对照中检测到了该突变(Fisher‘s确切检验：P<；0.01)。结论：我们的数据提供了确证的发现，在意大利人群中，PALB2有害突变是相对频繁的乳腺癌易感因素，可能与疾病的高风险有关。
Purpose: Monoallelic germ-line deleterious mutations of PALB2 (partner and localizer of BRCA2) are associated with breast cancer risk and have been found in several populations, with carrier frequencies of similar to 1-2%. Initially, these mutations were considered to have moderate penetrance, but accumulating evidence now indicates that they are associated with much higher risk.Methods: In this study, we sequenced the PALB2 coding regions unlinked to BRCA (breast cancer) genes in 575 probands from Italian breast cancer families recruited in Milan.Results: We found 12 carriers (2.1%) of deleterious mutations, and none of the mutations was found in 784 controls collected in Milan. One of these mutations, the c. 1027C>T (p.Gln343X), was found to be recurrent in the province of Bergamo in northern Italy, being detected in 6/113 (5.3%) familial breast cancer cases and 2/477 (0.4%) controls recruited in this area (Fisher's exact test: P < 0.01).Conclusions: Our data provide confirmatory findings that, in the Italian population also, deleterious mutations of PALB2 are relatively frequent predisposing factors for breast cancer and may be associated with high risk of the disease.