RT Journal Article
SR Electronic
T1 Biallelic Inactivation of hMLHl by Hypermethylation and Loss of Heterozygosity in Non-Small Cell Lung Cancer
JF Chinese Journal of Clinical Oncology
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 162
OP 165
VO 3
IS 3
A1 Geng, Xin
A1 Wang, Dong
A1 Zhu, Guoping
A1 Zhang, Liang
A1 Zhang, Weiming
YR 2006
UL http://www.cancerbiomed.org/content/3/3/162.abstract
AB OBJECTIVE To investigate the mechanism of hMLHl deregulation in non-small cell lung cancer (NSCLC).METHODS A genetic and epigenetic study of the hMLHl gene was performed using surgical primary tumors from 40 NSCLC patients and their corresponding noncancerous tissues. The molecular alterations examined included promoter méthylation by Hpa II/Msp I-based PCR analysis, loss of heterozygosity (LOH) by D3S1621 locus PCR-electrophore sis-silver staining, as well as the loss of protein expression by immunohistochemical analysis.RESULTS The frequencies of hypermthylation, LOH and loss of protein expression of hMLHl were 67.5% (27/40), 65% (26/40) and 72.5% (29/ 40), respectively. Among 26 hMLHl gene LOH (+) cases, 21 (80.8%) showed hypermthylation, which was significantly higher than the group of LOH (-). The frequency of the double inactivation of the hMLHl gene by hypermthylation and LOH related to a loss of protein expression of 72.4% (21/29).CONCLUSION Biallelic inactivation of the hMLHl gene by hypermthylation and LOH most likely will cause loss of hMLHl protein expression and play an Important role in the development of NSCLC. Therefore, controlling and monitoring for hypermthylation of the hMLHl gene may be partially useful for treatment and early diagnosis of NSCLC