title: CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer.
abstract: CpG island methylator phenotype (CIMP) involving methylation abnormalities of tumor suppressor gene (TSG) on short arm of chromosome 3 (chromosome 3p) has not been so far epigenetically elucidated in non-small cell lung cancer (NSCLC). Using methylation-specific PCR (MSP) method, we examined methylation profiles for eight TSGs harbored in chromosome 3p in 60 NSCLC tissues and 60 paired normal tissues as well as 11 normal blood samples. CIMP positive is referred to having four or more than four synchronously methylated genes per sample. Consequently, 59 of 60 (98.3%) NSCLC presented promoter methylation of at least one gene while only one malignant tumor showed no methylation of any of eight genes. The frequency of promoter methylation for eight genes explored ranged from 12% for hMLH1 to 67% for RASSF1A given that of VHL (none) was not considered. Interestingly, CIMP+ was found in 56.7% (34/60) of NSCLC, and in 6.7% (4/60) of paired normal tissues and 0% (0/11) of normal blood samples, respectively; CIMP- was present in 43.3% (26/60) of NSCLC, 93.3% (56/60) of paired normal tissues, and 100% (11/11) of normal blood samples, respectively. The data suggest that CIMP status was significantly associated with NSCLC, paired normal tissues and normal blood samples (P<0.001). In addition, there appeared to be a significant association between CIMP status and survival prognosis of NSCLC (P=0.0166). In the present study, for the first time, we shed light on the presence of chromosome 3p-specific CIMP, which might play an important role in tumorigenesis of NSCLC.
authors: Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren'ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China.
authors: Zeyi
authors: Z
authors: Liu
authors: Jun
authors: J
authors: Zhao
authors: Xiao-Feng
authors: XF
authors: Chen
authors: Wenwen
authors: W
authors: Li
authors: Rengyun
authors: R
authors: Liu
authors: Zhe
authors: Z
authors: Lei
authors: Xia
authors: X
authors: Liu
authors: Xiaobei
authors: X
authors: Peng
authors: Ke
authors: K
authors: Xu
authors: Jun
authors: J
authors: Chen
authors: Hongyu
authors: H
authors: Liu
authors: Qing-Hua
authors: QH
authors: Zhou
authors: Hong-Tao
authors: HT
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic