Koppert L B, Schutte M, Abbou M, Tilanus H W, Dinjens W N M
Department of Pathology, Erasmus university Medical Center, Josephine Nefkens Institute, PO Box 1738, Rotterdam 3000 DR, The Netherlands.
Br J Cancer. 2004 Feb 23;90(4):888-91. doi: 10.1038/sj.bjc.6601551.
In response to DNA damage, the cell cycle checkpoint kinase 2 (CHEK2) may phosphorylate p53, Cdc25A and Cdc25C, and regulate BRCA1 function, leading to cell cycle arrest and DNA repair. The truncating germline mutation CHEK2()1100delC abrogates kinase activity and confers low-penetrance susceptibility to breast cancer. We found CHEK2()1100delC in 0.5% of 190 oesophageal squamous cell carcinomas and in 1.5% of 196 oesophageal adenocarcinomas. In addition, we observed the mutation in 3.0% of 99 Barrett's metaplasias and 1.5% of 66 dysplastic Barrett's epithelia, both known precursor lesions of oesophageal adenocarcinoma. Since CHEK2()1100delC mutation frequencies did not significantly differ among oesophageal squamous cell carcinomas, adenocarcinomas and (dysplastic) Barrett's epithelia, as compared to healthy individuals, we conclude that the CHEK2()1100delC mutation has no major contribution in oesophageal carcinogenesis.
作为对DNA损伤的反应，细胞周期检查点激酶2（CHEK2）可能会使p53、细胞周期蛋白磷酸酶25A（Cdc25A）和细胞周期蛋白磷酸酶25C（Cdc25C）磷酸化，并调节乳腺癌1号基因（BRCA1）的功能，从而导致细胞周期停滞和DNA修复。截短的种系突变CHEK2()1100delC会消除激酶活性，并赋予乳腺癌低外显率易感性。我们在190例食管鳞状细胞癌的0.5%以及196例食管腺癌的1.5%中发现了CHEK2()1100delC。此外，我们在99例巴雷特化生的3.0%以及66例发育异常的巴雷特上皮的1.5%中观察到了该突变，这两者都是已知的食管腺癌前体病变。由于与健康个体相比，食管鳞状细胞癌、腺癌以及（发育异常的）巴雷特上皮中CHEK2()1100delC的突变频率没有显著差异，我们得出结论，CHEK2()1100delC突变在食管癌发生过程中没有主要作用。
