Gene Implicated in Both Hereditary and Sporadic Lung Cancers

Genetic fine mapping has revealed that the RGS17 gene, which is located in the major familial lung cancer susceptibility locus on chromosome 6q23-25, is also overexpressed in many cases of nonhereditary lung cancer.

Previous genetic mapping studies had identified a major susceptibility locus influencing familial lung cancer risk on chromosome 6q23-25. However, the causal gene at this locus was not determined. In the current study, investigators 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). They mapped the susceptibility locus in lung tissue samples obtained from six multigenerational families with five or more affected members.

Results published in the April 15, 2009, issue of the journal Clinical Cancer Research revealed significant association between lung cancer susceptibility and three single nucleotide polymorphisms in the first intron of the RGS17 gene.

To confirm the role of RGS17 in tumor development the investigators created a line of mice lacking the gene. They found that growth of transplanted human lung cancer cells was strongly inhibited in the "knock-down" mice.

"Understanding how the RGS17 gene impacts cancer development could change clinical diagnosis and treatment as radically as discovery of the breast cancer genes (BRCA1 and BRCA2) did," explained senior author Dr. Marshall Anderson, professor of molecular oncogenesis at the University of Cincinnati (OH, USA). "What was most interesting is that this same gene was overexpressed in 60% of the samples from nonhereditary lung tumors. This suggests that perhaps epigenetic factors may be contributing to abnormal genetic development. A proven genetic test could help us identify people at risk before the disease progresses."

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