Cao A-Yong, Huang Juan, Hu Zhen, Li Wen-Feng, Ma Zhong-Liang, Tang Li-Li, Zhang Bin, Su Feng-Xi, Zhou Jie, Di Gen-Hong, Shen Kun-Wei, Wu Jiong, Lu Jin-Song, Luo Jian-Min, Yuan Wen-Tao, Shen Zhen-Zhou, Huang Wei, Shao Zhi-Ming
Breast Cancer Institute, Cancer Hospital/Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, People's Republic of China.
Breast Cancer Res Treat. 2009 Apr;114(3):457-62. doi: 10.1007/s10549-008-0036-z. Epub 2008 Apr 30.
PALB2 has been recently identified as breast cancer susceptibility gene in western populations. To investigate the contribution of PALB2 mutations to Chinese non-BRCA1/BRCA2 hereditary breast cancer, we screened all coding exons and intron-exon boundaries of PALB2 in 360 Chinese women with early-onset breast cancer or affected relatives from five breast disease clinical centers in China by utilizing PCR-DHPLC and DNA sequencing analysis. Some genetic variants identified in the cases were then studied in 864 normal controls with no personal or family history of breast cancer. Two protein-truncating PALB2 mutations, 751C>T and 1050_1051delAAinsTCT, were identified in three separate families, and 751C>T was a recurrent mutation. Neither of them, however, were present in the controls (P=0.025). All the truncating mutations occurred in exon 4 of PALB2, and there were still three unclassified variants were detected in the same fragment. We found that exon 4 accounted for 44.1% (15/34) of the person-times carrying with any variant in our study. PALB2 mutations were responsible for approximately 1% of Chinese women with early-onset breast cancer and affected relatives. Our results suggested that a detection of exon 4 before the assay of the whole PALB2 gene might be a cost-effective approach to the screening of Chinese population.
PALB2最近在西方人群中被鉴定为乳腺癌易感基因。为了研究PALB2突变对中国非BRCA1/BRCA2遗传性乳腺癌的影响，我们通过聚合酶链反应-变性高效液相色谱（PCR-DHPLC）和DNA测序分析，对来自中国五个乳腺疾病临床中心的360名早发性乳腺癌中国女性或其患病亲属的PALB2所有编码外显子和内含子-外显子边界进行了筛查。然后，在864名无乳腺癌个人或家族史的正常对照中研究了在病例中鉴定出的一些基因变异。在三个不同的家族中鉴定出两个导致蛋白质截短的PALB2突变，即751C>T和1050_1051delAAinsTCT，其中751C>T是一个复发性突变。然而，在对照中均未发现这两个突变（P=0.025）。所有截短突变均发生在PALB2的第4外显子中，并且在同一片段中仍检测到三个未分类的变异。我们发现，在我们的研究中，第4外显子占携带任何变异的人次的44.1%（15/34）。PALB2突变约占中国早发性乳腺癌女性及其患病亲属的1%。我们的结果表明，在检测整个PALB2基因之前先检测第4外显子，可能是一种筛查中国人群的经济有效的方法。
