Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.

TitleIdentification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.
Publication TypeJournal Article
Year of Publication2007
AuthorsWang, M, Vikis, HG, Wang, Y, Jia, D, Wang, D, Bierut, LJ, Bailey-Wilson, JE, Amos, CI, Pinney, SM, Petersen, GM, de Andrade, M, Yang, P, Wiest, JS, Fain, PR, Schwartz, AG, Gazdar, A, Minna, J, Gaba, C, Rothschild, H, Mandal, D, Kupert, E, Seminara, D, Liu, Y, Viswanathan, A, Govindan, R, Anderson, MW, You, M
JournalCancer Res
Volume67
Issue1
Pagination93-9
Date Published2007 Jan 01
ISSN0008-5472
KeywordsAlleles, Animals, Base Sequence, Chromosomes, Human, Pair 6, Codon, Female, Genes, Tumor Suppressor, Genetic Predisposition to Disease, Humans, Loss of Heterozygosity, Lung Neoplasms, Mice, Mice, Nude, Molecular Sequence Data, Polymorphism, Single Nucleotide
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.

DOI10.1158/0008-5472.CAN-06-2723
Alternate JournalCancer Res.
PubMed ID17210687
PubMed Central IDPMC3461257
Grant ListR01 CA084354 / CA / NCI NIH HHS / United States
R01 ES013340 / ES / NIEHS NIH HHS / United States
R01 CA 80127 / CA / NCI NIH HHS / United States
P01 CA089392 / CA / NCI NIH HHS / United States
U01 CA076293 / CA / NCI NIH HHS / United States
R01 CA080127 / CA / NCI NIH HHS / United States
R01 CA 84354 / CA / NCI NIH HHS / United States
ZIA BC010448-09 / NU / Intramural NIH HHS / United States
R01 ES 013340 / ES / NIEHS NIH HHS / United States
R01 CA 099187 / CA / NCI NIH HHS / United States
P30 ES006096 / ES / NIEHS NIH HHS / United States
R01 CA099147 / CA / NCI NIH HHS / United States
P01 CA 89392 / CA / NCI NIH HHS / United States
P50 CA 70907 / CA / NCI NIH HHS / United States
P50 CA070907 / CA / NCI NIH HHS / United States
R01 ES 012063 / ES / NIEHS NIH HHS / United States
R01 CA099187 / CA / NCI NIH HHS / United States
R01 ES012063 / ES / NIEHS NIH HHS / United States
U01 CA 76293 / CA / NCI NIH HHS / United States
R01 CA 099147 / CA / NCI NIH HHS / United States