Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.
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.
Wang
Min
M
School of Medicine, Washington University, 660 Euclid Avenue, St. Louis, MO, USA.
Vikis
Haris G
HG
Wang
Yian
Y
Jia
Dongmei
D
Wang
Daolong
D
Bierut
Laura J
LJ
Bailey-Wilson
Joan E
JE
Amos
Christopher I
CI
Pinney
Susan M
SM
Petersen
Gloria M
GM
de Andrade
Mariza
M
Yang
Ping
P
Wiest
Jonathan S
JS
Fain
Pamela R
PR
Schwartz
Ann G
AG
Gazdar
Adi
A
Minna
John
J
Gaba
Colette
C
Rothschild
Henry
H
Mandal
Diptasri
D
Kupert
Elena
E
Seminara
Daniela
D
Liu
Yan
Y
Viswanathan
Avinash
A
Govindan
Ramaswamy
R
Anderson
Marshall W
MW
You
Ming
M
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
D003062:Codon