Complex genetic control of lung tumorigenesis in resistant mice strains
| Autor: | Tommaso A. Dragani, Andrea Borrego, Elena Forcati, Giulia Pintarelli, Alice Dassano, Giacomo Manenti, Francesca Colombo, Loris De Cecco, Angela Pettinicchio, Chiara E. Cotroneo |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cancer Research Lung Neoplasms Genotype Carcinogenesis Locus (genetics) Mice Inbred Strains Quantitative trait locus Biology Polymorphism Single Nucleotide Pas1 03 medical and health sciences Mice Inbred strain Genetic linkage medicine Animals Humans Genetic Predisposition to Disease Allele Lung cancer Genetics Genomics and Proteomics Alleles Genetic Association Studies Genetics Haplotype genetic loci General Medicine Original Articles medicine.disease Disease Models Animal lung cancer 030104 developmental biology Oncology Chromosome 3 Haplotypes quantitative trait loci Original Article Female |
| Zdroj: | Cancer science 108 (2017): 2281–2286. doi:10.1111/cas.13349 info:cnr-pdr/source/autori:Dassano, Alice; Pintarelli, Giulia; Cotroneo, Chiara E.; Pettinicchio, Angela; Forcati, Elena; De Cecco, Loris; Borrego, Andrea; Colombo, Francesca; Dragani, Tommaso A.; Manenti, Giacomo/titolo:Complex genetic control of lung tumorigenesis in resistant mice strains/doi:10.1111%2Fcas.13349/rivista:Cancer science/anno:2017/pagina_da:2281/pagina_a:2286/intervallo_pagine:2281–2286/volume:108 Cancer Science |
| Popis: | The SM/J mouse strain is resistant to chemically-induced lung tumorigenesis despite having a haplotype, in the pulmonary adenoma susceptibility locus (Pas1) locus, that confers tumor susceptibility in other strains. To clarify this inconsistent genotype-phenotype correlation, we crossed SM/J mice with another resistant strain and conducted genome-wide linkage analysis in the (C57BL/6J × SM/J)F2 progeny exposed to urethane to induce lung tumors. Overall, >80% of F2 mice of both sexes developed from 1 to 20 lung tumors. Genotyping of 372 F2 mice for 744 informative non-redundant SNPs dispersed over all autosomal chromosomes revealed four quantitative trait loci (QTLs) affecting lung tumor multiplicity, on chromosomes 3 (near rs13477379), 15 (rs6285067), 17 (rs33373629) and 18 (rs3706601), all with logarithm of the odds (LOD) scores >5. Four QTLs modulated total lung tumor volume, on chromosome 3 (rs13477379), 10 (rs13480702), 15 (rs6285067) and 17 (rs3682923), all with LOD scores >4. No QTL modulating lung tumor multiplicity or total volume was detected in Pas1 on chromosome 6. The present study demonstrates that the SM/J strain carries, at the Pas1 locus, the resistance allele: a finding that will facilitate identification of the Pas1 causal element. More generally, it demonstrates that lung tumorigenesis is under complex polygenic control even in a pedigree with low susceptibility to this neoplasia, suggesting that the genetics of lung tumorigenesis is much more complex than evidenced by the pulmonary adenoma susceptibility and resistance loci that have, so far, been mapped in a small number of crosses between a few inbred strains. |
| Databáze: | OpenAIRE |
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