Phuah Sze Yee, Lee Sheau Yee, Kang Peter, Kang In Nee, Yoon Sook-Yee, Thong Meow Keong, Hartman Mikael, Sng Jen-Hwei, Yip Cheng Har, Taib Nur Aishah Mohd, Teo Soo-Hwang
Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
PLoS One. 2013 Aug 20;8(8):e73638. doi: 10.1371/journal.pone.0073638. eCollection 2013.
The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.
We evaluated the contribution of PALB2 germline mutations in 122 Asian women with breast cancer, all of whom had significant family history of breast and other cancers. Further screening for nine PALB2 mutations was conducted in 874 Malaysian and 532 Singaporean breast cancer patients, and in 1342 unaffected Malaysian and 541 unaffected Singaporean women.
By analyzing the entire coding region of PALB2, we found two novel truncating mutations and ten missense mutations in families tested negative for BRCA1/2-mutations. One additional novel truncating PALB2 mutation was identified in one patient through genotyping analysis. Our results indicate a low prevalence of deleterious PALB2 mutations and a specific mutation profile within the Malaysian and Singaporean populations.
乳腺癌2的伴侣和定位蛋白（PALB2）通过作为桥梁分子，在乳腺癌1（BRCA1）和乳腺癌2（BRCA2）蛋白之间起物理和功能连接作用，从而促进BRCA2介导的DNA修复。PALB2基因的截短突变很少见，但被认为与不同人群患乳腺癌的风险增加有关。
我们评估了122名亚洲乳腺癌女性中PALB2种系突变的作用，所有这些女性都有显著的乳腺癌和其他癌症家族史。对874名马来西亚和532名新加坡乳腺癌患者以及1342名未受影响的马来西亚女性和541名未受影响的新加坡女性进一步筛查了9种PALB2突变。
通过分析PALB2的整个编码区，我们在BRCA1/2突变检测呈阴性的家族中发现了两个新的截短突变和十个错义突变。通过基因分型分析在一名患者中鉴定出另外一个新的截短PALB2突变。我们的结果表明有害的PALB2突变在马来西亚和新加坡人群中的患病率较低，且存在特定的突变谱。
