Paulson Thomas G, Galipeau Patricia C, Xu Lianjun, Kissel Heather D, Li Xiaohong, Blount Patricia L, Sanchez Carissa A, Odze Robert D, Reid Brian J
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2008;3(11):e3809. doi: 10.1371/journal.pone.0003809. Epub 2008 Nov 27.
Mutation, promoter hypermethylation and loss of heterozygosity involving the tumor suppressor gene p16 (CDKN2a/INK4a) have been detected in a wide variety of human cancers, but much less is known concerning the frequency and spectrum of p16 mutations in premalignant conditions.
We have determined the p16 mutation spectrum for a cohort of 304 patients with Barrett's esophagus, a premalignant condition that predisposes to the development of esophageal adenocarcinoma. Forty seven mutations were detected by sequencing of p16 exon 2 in 44 BE patients (14.5%) with a mutation spectrum consistent with that caused by oxidative damage and chronic inflammation. The percentage of patients with p16 mutations increased with increasing histologic grade. In addition, samples from 3 out of 19 patients (15.8%) who underwent esophagectomy were found to have mutations.
The results of this study suggest the environment of the esophagus in BE patients can both generate and select for clones with p16 mutations.
在多种人类癌症中均检测到涉及肿瘤抑制基因p16（CDKN2a/INK4a）的突变、启动子高甲基化和杂合性缺失，但对于癌前病变中p16突变的频率和谱了解较少。
我们确定了304例巴雷特食管患者队列的p16突变谱，巴雷特食管是一种易发展为食管腺癌的癌前病变。通过对44例（14.5%）巴雷特食管患者的p16外显子2进行测序检测到47个突变，其突变谱与氧化损伤和慢性炎症所致的一致。p16突变患者的百分比随组织学分级增加而升高。此外，在19例接受食管切除术的患者中，有3例（15.8%）的样本被发现存在突变。
本研究结果提示，巴雷特食管患者的食管环境既能产生也能选择具有p16突变的克隆。
