Mohamad Suriati, Isa Nurismah Md, Muhammad Rohaizak, Emran Nor Aina, Kitan Nor Mayah, Kang Peter, Kang In Nee, Taib Nur Aishah Mohd, Teo Soo Hwang, Akmal Sharifah Noor
Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur, Malaysia.
PLoS One. 2015 Jan 28;10(1):e0117104. doi: 10.1371/journal.pone.0117104. eCollection 2015.
CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population.
CHEK2是一种蛋白激酶，参与DNA损伤后的细胞周期检查点控制。CHEK2基因的种系突变与乳腺癌风险增加有关。本研究的目的是确定高危乳腺癌患者中的CHEK2基因种系突变及其对马来西亚多民族人群的影响。我们对来自马来西亚国立大学医学中心（UKMMC）、吉隆坡医院（HKL）和布城医院（HPJ）的59例BRCA1/2种系突变检测为阴性的高危乳腺癌患者的CHEK2基因整个编码区进行了筛查。在由878例未经选择的浸润性乳腺癌患者（180例马来人、526例中国人和172例印度人）和270名健康个体（90例马来人、90例中国人和90例印度人）组成的病例对照队列中，对鉴定出的序列变异进行了进一步筛查。通过筛查CHEK2基因的整个编码区，在两名无关患者中鉴定出两个错义突变，即c.480A>G（p.I160M）和c.538C>T（p.R180C）（3.4%）。在病例对照队列中对这些错义突变进行进一步筛查发现，变异p.I160M在2/172（1.1%）的印度病例和1/90（1.1%）的印度对照中出现，变异p.R180C在2/526（0.38%）的中国病例和0/90的中国对照中出现，以及在2/180（1.1%）的马来病例和1/90（1.1%）的马来对照中出现。本研究结果表明，CHEK2突变在高危乳腺癌患者中罕见，可能在马来西亚人群的乳腺癌发生中起次要作用。
