Title: Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.
Authors: Wang, Min; Vikis, Haris G; Wang, Yian; Jia, Dongmei; Wang, Daolong; Bierut, Laura J; Bailey-Wilson, Joan E; Amos, Christopher I; Pinney, Susan M; Petersen, Gloria M; de Andrade, Mariza; Yang, Ping; Wiest, Jonathan S; Fain, Pamela R; Schwartz, Ann G; Gazdar, Adi; Minna, John; Gaba, Colette; Rothschild, Henry; Mandal, Diptasri; Kupert, Elena; Seminara, Daniela; Liu, Yan; Viswanathan, Avinash; Govindan, Ramaswamy; Anderson, Marshall W; You, Ming
Published In Cancer Res, (2007 Jan 01)
Abstract: In this study, we observed loss of heterozygosity (LOH) in human chromosomal fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the 26 lung tumors examined and was narrowed down to a 2.2-Mb region. Single-nucleotide polymorphism (SNP) analysis of genes located within this region identified a candidate gene, termed p34. This gene, also designated as ZC3H12D, C6orf95, FLJ46041, or dJ281H8.1, carries an A/G nonsynonymous SNP at codon 106, which alters the amino acid from lysine to arginine. Nearly 73% of heterozygous lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele. In vitro clonogenic and in vivo nude mouse studies showed that overexpression of the A allele exerts tumor suppressor function compared with the G allele. p34 is located within a recently mapped human lung cancer susceptibility locus, and association of the p34 A/G SNP was tested among these families. No significant association between the less frequent G allele and lung cancer susceptibility was found. Our results suggest that p34 may be a novel tumor suppressor gene involved in sporadic lung cancer but it seems not to be the candidate familial lung cancer susceptibility gene linked to chromosomal region 6q23-25.
PubMed ID: 17210687
MeSH Terms: Alleles; Animals; Base Sequence; Chromosomes, Human, Pair 6*; Codon; Female; Genes, Tumor Suppressor*; Genetic Predisposition to Disease; Humans; Loss of Heterozygosity*; Lung Neoplasms/genetics*; Mice; Mice, Nude; Molecular Sequence Data; Polymorphism, Single Nucleotide