Uncovering New Links to Lung Cancer in Mice
For years, scientists have been hunting for genes involved in different types of lung cancer, such as pulmonary adenocarcinoma and squamous cell carcinoma. However, smoking and other environmental factors can obscure the genetic basis of human lung cancers, making animal models important for researchers in the field. In the July issue of Genome Research, Giacomo Manenti, Tommaso Dragani (both at the Istituto Nazionale Tumori, Milan), and colleagues report mapping a pulmonary adenoma susceptibility locus (Pas1) to a restricted region of mouse chromosome 6, laying the basis for cloning the mouse Pas1 gene and providing essential clues for identifying similar genes in humans.
The researchers employed a method for locating disease genes called linkage disequilibrium (LD), an approach previously applied chiefly to human populations. In LD, scientists scan for unique DNA markers that occur more frequently in affected individuals than in normal individuals. Markers displaying strong linkage with a disease may indicate the location of responsible genes. By comparing markers from strains of mice susceptible to lung tumors to markers from tumor resistant strains, Manenti and colleagues pinpointed a group of markers linked to pulmonary adenomas and placed the Pas1 locus to within 1.5 megabases on mouse chromosome 6. They also found that the different susceptible strains likely inherited their Pas1 mutations from the same ancestral source, a discovery that will facilitate cloning the Pas1 lung cancer gene in mice.
Tommaso A. Dragani
Department of Experimental Oncology
Istituto Nazionale Tumori
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