title: Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.
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.
authors.affiliation: School of Medicine, Washington University, 660 Euclid Avenue, St. Louis, MO, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Haris G
authors.initials: HG
authors.lastname: Vikis
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Jia
authors.forename: Daolong
authors.initials: D
authors.lastname: Wang
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Susan M
authors.initials: SM
authors.lastname: Pinney
authors.forename: Gloria M
authors.initials: GM
authors.lastname: Petersen
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wiest
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Fain
authors.forename: Ann G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Adi
authors.initials: A
authors.lastname: Gazdar
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: Colette
authors.initials: C
authors.lastname: Gaba
authors.forename: Henry
authors.initials: H
authors.lastname: Rothschild
authors.forename: Diptasri
authors.initials: D
authors.lastname: Mandal
authors.forename: Elena
authors.initials: E
authors.lastname: Kupert
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Avinash
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Anderson
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002896:Chromosomes, Human, Pair 6; D003062:Codon; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
chemical_list: D003062:Codon