Identification of Lung Tumor Susceptibility Genes

Ming You, MD, Ph.D.
Washington University School of Medicine
R01ES12063 and R01ES 13340

Ming You of the Washington University School of Medicine reports in the August edition of Nature Genetics the discovery of new lung cancer susceptibility genes along with advances in the technique of whole-genome association analyses to identify candidate genes. Whole-genome association studies are a comprehensive approach to testing the hypothesis that common alleles contribute to genetically inherited diseases.

Using inbred mice, You and his research team reproduced the pulmonary adenoma susceptibility 1 (Pas1) locus previously identified in other studies. There efforts narrowed this locus to a region of DNA less than 500,000 bases which contains at least two genes that are strong lung-cancer susceptibility gene candidates. Then using knock-out mice, transgenic mice missing these genes, the team found that cancer susceptibility candidate 1 (Casc1) knock-out mice are susceptible to chemical induction of lung-tumors. They also identified three other locations for possible lung cancer genes. One of these genes, named lung adenoma susceptibility candidate 1 (Lasc1) was previously unknown. They also determined that a specific allele of this gene "preferentially promotes lung tumor cell growth."

These findings are significant because they represent progress in identifying genes whose human forms may predispose some individuals to lung cancer. They also demonstrate that as new resources and denser single nucleotide polymorphism maps become available, mouse models of human diseases will be central to disease susceptibility gene discovery in whole-genome association analyses.

Citation: Liu P, Wang Y, Vikis H, Maciag A, Wang D, Lu Y, Liu Y, You M. Candidate lung tumor susceptibility genes identified through whole-genome association analyses in inbred mice. Nat Genet. 2006 Aug;38(8):888-95.