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Identification of a Novel Tumor Suppressor Gene p34 on Human Chromosome 6q25.1

¹ Washington University, St. Louis, Missouri; ² National Human Genome Research Institute, Bethesda, Maryland; ³ M.D. Anderson Cancer Center, Houston, Texas; ⁴ University of Cincinnati, Cincinnati, Ohio; ⁵ Mayo Clinic College of Medicine, Rochester, Minnesota; ⁶ National Cancer Institute, Rockville, Maryland; ⁷ University of Colorado, Denver, Colorado; ⁸ Karmanos Cancer Institute, Detroit, Michigan; ⁹ University of Texas Southwestern Medical Center, Dallas, Texas; ¹⁰ Medical University of Ohio, Toledo, Ohio; and ¹¹ Louisiana State University Health Science Center, New Orleans, Louisiana

Requests for reprints: Ming You, Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 Euclid Avenue, Box 8109, St. Louis, MO. Phone: 314-362-9294; Fax: 314-362-9366; E-mail: youm{at}wustl.edu.

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. [Cancer Res 2007;67(1):93–9]

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