Citations 2
Fine Mapping of Chromosome 6q23-25 Region in Familial Lung Cancer Families Reveals RGS17 as a Likely Candidate Gene
You, Ming , Wang, Daolong, Liu, Pengyuan , Vikis, Haris G., James, Michael A. , Wang, Yian , Jia, Dongmei , Wen, Weidong, Sun, Zhifu , Pinney, Susan M. , Zheng, Wei , Shu, Xiao‐Ou , Long, Jirong , Gao, Yu-Tang, Xiang, Yong-Bing , Chow, Wong‐Ho , Rothman, Nat, Petersen, Gloria M. , Cunningham, Julie M. , Wiest, Jonathan S., Fain, Pamela R., Schwartz, Ann G. , Girard, Luc , Gazdar, Adi, Gaba, Colette , Rothschild, Henry, Mandal, Diptasri , Coons, Teresa, Lee, Juwon , Kupert, Elena, Seminara, Daniela, Bailey‐Wilson, Joan E. , Anderson, Marshall W., Lü, Yan , Wang, Min , Chen, Qiong , Liu, Yan , Yang, Ping , Andrade, Mariza de , Wu, Yanhong , Minna, John Dorrance , Amos, Christopher I. , Sun, Zhifu , Wilson, Richard K , Shu, Xiao-Ou , Zheng, Wei , Pinney, Susan M
Clinical Cancer Research | April 7, 2009 | Volume: 15 | Issue: 8 | Pages: 2666-2674
Abstract Purpose: We have previously mapped a major susceptibility locus influencing familial lung cancer risk to chromosome 6q23-25. However, the causal gene at this locus remains undetermined. In this study, we further refined this locus to identify a single candidate gene, by fine mapping using microsatellite markers and association studies using high-density single nucleotide polymorphisms (SNP). Experimental Design: Six multigenerational families with five or more affected members were chosen for fine-mapping the 6q linkage region using microsatellite markers. For association mapping, we genotyped 24 6q-linked cases and 72 unrelated noncancer controls from the Genetic Epidemiology of Lung Cancer Consortium resources using the Affymetrix 500K chipset. Significant associations were validated in two independent familial lung cancer populations: 226 familial lung cases and 313 controls from the Genetic Epidemiology of Lung Cancer Consortium, and 154 familial cases and 325 controls from Mayo Clinic. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members. Results: A region-wide scan across 6q23-25 found significant association between lung cancer susceptibility and three single nucleotide polymorphisms in the first intron of the RGS17 gene. This association was further confirmed in two independent familial lung cancer populations. By quantitative real-time PCR analysis of matched tumor and normal human tissues, we found that RGS17 transcript accumulation is highly and consistently increased in sporadic lung cancers. Human lung tumor cell proliferation and tumorigenesis in nude mice are inhibited upon knockdown of RGS17 levels. Conclusion: RGS17 is a major candidate for the familial lung cancer susceptibility locus on chromosome 6q23-25.
Identification of a Novel Tumor Suppressor Gene p34 on Human Chromosome 6q25.1
Vikis, Haris G., Wang, Yian , Jia, Dongmei , Wang, Daolong, Bailey‐Wilson, Joan E. , Pinney, Susan M. , Petersen, Gloria M. , Wiest, Jonathan S., Fain, Pamela R., Schwartz, Ann G. , Gazdar, Adi F., Gaba, Colette , Rothschild, Henry, Mandal, Diptasri , Kupert, Elena, Seminara, Daniela, Liu, Yan , Viswanathan, Avinash, Govindan, Ramaswamy , Anderson, Marshall W., You, Ming , Wang, Min , Bierut, Laura Jean , Amos, Christopher I. , Andrade, Mariza de , Yang, Ping , Gazdar, Adi, Minna, John Dorrance , Wilson, Richard K , Pinney, Susan M , Govindan, Ramaswamy
Cancer Research | January 8, 2007 | Volume: 67 | Issue: 1 | Pages: 93-99
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. [Cancer Res 2007;67(1):93–9]