title: High frequency somatic mutations in RASSF1A in nasopharyngeal carcinoma.
abstract: 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.
authors.affiliation: Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Pan
authors.forename: V I
authors.initials: VI
authors.lastname: Kashuba
authors.forename: Xiao-Qiong
authors.initials: XQ
authors.lastname: Liu
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Ru-Hua
authors.initials: RH
authors.lastname: Zhang
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jiang
authors.forename: Can
authors.initials: C
authors.lastname: Guo
authors.forename: Eugene
authors.initials: E
authors.lastname: Zabarovsky
authors.forename: Ingemar
authors.initials: I
authors.lastname: Ernberg
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
mesh_terms: 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*
chemical_list: C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins