High frequency somatic mutations in RASSF1A in nasopharyngeal carcinoma.
High frequency loss of 3p21.3 region is a common event in various kinds of tumors including nasopharyngeal carcinoma (NPC). RASSF1A has been identified as a putative tumor suppressor gene residing in this region. Chromosome alterations and epigenetic changes are commonly observed as mechanisms for inactivation of RASSF1A function. In this study, we applied the PCR-cloning-sequencing strategy to examine somatic mutations in RASSF1A in NPC tissues as compared with the sequences detected in the matched peripheral blood lymphocytes. Our results revealed a high incidence of RASSF1A mutation in primary tumor tissues of NPC. There are totally 35 mutations identified in 74% (17/23) of these NPC cases, including 30 transitions, three transversions and two deletions. Most of these mutations result in amino acid changes: three nonsense (stop codon) mutations, two-1 bp deletion (frameshift), 26 missense and the remaining four are synonymous (silent). No obvious 'hot-spot' mutations were observed in this study. A similarly high rate (74%) of promoter methylation of RASSF1A was also detected in the same group of NPC tissues, but no significant correlation between mutation and methylation was detected. Our results suggest various mechanisms involved in inactivation of RASSF1A function and indicate a critical role of RASSF1A in NPC development.
Pan
Zhi-Gang
ZG
Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Kashuba
V I
VI
Liu
Xiao-Qiong
XQ
Shao
Jian-Yong
JY
Zhang
Ru-Hua
RH
Jiang
Ju-Hong
JH
Guo
Can
C
Zabarovsky
Eugene
E
Ernberg
Ingemar
I
Zeng
Yi-Xin
YX
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000473:pathology*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins