Maesawa C, Tamura G, Nishizuka S, Ogasawara S, Ishida K, Terashima M, Sakata K, Sato N, Saito K, Satodate R
Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
Cancer Res. 1996 Sep 1;56(17):3875-8.
We examined the genomic status of the CDKN2 gene including de novo methylation of 5' CpG islands in primary and metastatic tumor samples from 31 patients with esophageal squamous cell carcinoma. One somatic frame shift mutation (1 of 31; 3.2%) was identified by PCR-single strand conformational polymorphism analysis and DNA sequencing. Homozygous deletion and de novo methylation of the gene were confirmed in 5 (16%) and 6 (19%) of 31 patients, respectively. Homozygous deletion and de novo methylation were significantly associated with silencing of gene expression (P < 0.01). Aberrations of the CDKN2 gene were detected in tumors with lymph node metastasis and muscular invasion (12 of 22; 54%) and in none of stage I tumors (0 of 9.0%; P < 0.05). These results suggest that homozygous deletion and de novo methylation are predominant mechanisms of inactivation of the CDKN2 gene and may be associated with metastatic and invasive phenotypes of esophageal squamous cell carcinoma.
我们检测了31例食管鳞状细胞癌患者原发及转移肿瘤样本中CDKN2基因的基因组状态，包括5' CpG岛的从头甲基化。通过PCR-单链构象多态性分析和DNA测序鉴定出1例体细胞移码突变（31例中的1例；3.2%）。在31例患者中，分别有5例（16%）和6例（19%）证实存在该基因的纯合缺失和从头甲基化。纯合缺失和从头甲基化与基因表达沉默显著相关（P < 0.01）。在有淋巴结转移和肌层浸润的肿瘤中检测到CDKN2基因异常（22例中的12例；54%），而在I期肿瘤中未检测到（9例中的0例；P < 0.05）。这些结果表明，纯合缺失和从头甲基化是CDKN2基因失活的主要机制，可能与食管鳞状细胞癌的转移和侵袭表型相关。
