[Expression, loss of heterozygosity, and methylation of GNAT1 gene in nasopharyngeal carcinoma].
OBJECTIVE
In nasopharyngeal carcinoma (NPC), chromosome 3p21.3 is a high frequency deletion region. Evidences from both loss of heterozygosity (LOH) and functional studies showed that there may exists NPC-related tumor suppressor genes on 3p21.3. This study was to investigate the expression, LOH, and methylation of GNAT1 gene, which locates at 3p21.3, in NPC.


METHODS
The expression of GNAT1 in 33 specimens of primary NPC and 15 specimens of chronic nasopharyngitis tissue was detected by reverse transcription-polymerase chain reaction (RT-PCR). LOH and promoter methylation status of GNAT1 were examined by microsatellites analysis and methylation-specific polymerase chain reaction (MSP).


RESULTS
GNAT1 was expressed stably in all chronic nasopharyngitis tissues, while absent or down-regulated in 24 (72.7%) specimens of NPC (P=0.022). LOH analysis showed allele loss of GNAT1 in 3 (15%) specimens of NPC. LOH of GNAT1 was correlated to its expression level (P=0.016). Methylation analysis showed hypermethylation of GNAT1 promoter in all primary NPC tissues and in 12 (80%) specimens of chronic nasopharyngitis tissues.


CONCLUSIONS
Expression of GNAT1 gene is down-regulated or absent in NPC tissues, which may relate to allele loss of GNAT1 in NPC, but not relate to its promoter hypermethylation. Hypermethylation of GNAT1 may not be oncogenic mechanisms of NPC.
Yi
Hong-Mei
HM
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, P. R. China.
Ren
Cai-Ping
CP
Peng
Dan
D
Zhou
Liang
L
Li
Hui
H
Yao
Kai-Tai
KT
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020962:Heterotrimeric GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015293:Transducin
D004273:DNA, Neoplasm; C034809:GNAT1 protein, human; D012333:RNA, Messenger; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin