CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer

Liu, Zeyi; Zhao, Jun; Chen, Xiao-Feng; Li, Wenwen; Liu, Rengyun; Lei, Zhe; Liu, Xia; Peng, Xiaobei; Xu, Ke; Chen, Jun; Liu, Hongyu; Zhou, Qing-Hua; Zhang, Hong-Tao

doi:10.1016/j.lungcan.2008.02.005

« Previous Next »Lung Cancer
Volume 62, Issue 1 , Pages 15-22, October 2008

CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer

Zeyi Liu
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
Jun Zhao
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
- The First Affiliated Hospital, Suzhou University, Suzhou, PR China
Xiao-Feng Chen
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
- Department of Surgery, Shanghai Hospital for Pulmonary Diseases, Shanghai, PR China
Wenwen Li
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
Rengyun Liu
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
Zhe Lei
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
Xia Liu
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
Xiaobei Peng
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
Ke Xu
- Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, PR China
Jun Chen
- Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, PR China
Hongyu Liu
- Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, PR China
Qing-Hua Zhou
- Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, PR China
- Corresponding author. Tel.: +86 22 60363020; fax: +86 22 60363013.
Hong-Tao Zhang
- Laboratory of Medical Genetics, School of Basic Medicine & Biological Sciences, Suzhou University, 199 Ren’ai Road, Sino-Singapore Industrial Park, 215123 Suzhou, PR China
- Corresponding author. Tel.: +86 512 65882809; fax: +86 512 65584083.

Received 22 November 2007; received in revised form 15 January 2008; accepted 5 February 2008. published online 25 March 2008.

Summary

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.