Experiment
Whole genome linkage disequilibrium analysis was performed on 7 inbred strains of mice to identify QTLs associated with susceptibility to lung squamous cell carcinoma (LSCC). 6,128 markers were screened. Lung squamous cell carcinoma was induced with N-nitroso-trischloroethylurea (NTCU) via skin painting. Inbred strains AKR/J, 129X1/SvJ, and C57BL/6J are resistant to NTCU-induced LSCC. The intermediate susceptible inbred strains are BALB/cJ and FVB/J, and the susceptible inbred strains are NIH Swiss, SWR/J, and A/J.
Significant linkage was detected at 15 cM on mouse Chromosome 1 at D1Mit169. This locus is named Lscc1 (lung squamous cell carcinoma 1). A search for candidate genes was conducted within 2.5 cM of Lscc1 between markers D1Mit52 (12 cM) and D1Mit526 (17.8 cM). Potential candidate genes include Il17, Mcm3, Gsta3, and Bai3. Authors also indicated Il17f as a candidate but this gene has not yet been identified in mouse. Lscc1 maps near previously identified lung cancer QTL Sluc15 (19.5 cM).
Lscc2 mapped to 13.8 cM on mouse Chromosome 3 at D3Mit178. A search for candidate genes was conducted within 2.5 cM of Lscc2 between markers D3Mit203 (11.2 cM) and D3Mit167 (16.5 cM). Potential candidate genes include Ect2, Ghsr, Pld1, Slc2a2, Evi1, Mds1, Prkci,Skil, Tnfsf10, and Cldn11. Lscc2 is syntenic to human chromosome 3q26, a region that has been associated with squamous cell carcinoma in humans.
Lscc3 mapped to 29 cM on mouse Chromosome 18 at D18Mit91. A search for candidate genes was conducted within 2.5 cM of Lscc3 between markers D18Mit10 (26 cM) and D18Mit52 (32 cM). Potential candidate genes include Lmnb1 and Slc12a2. Lscc1 maps near previously identified colon tumor QTL Scc5 (25 cM) and previously identified lung cancer QTL Sluc14 (20 cM).