Identification of fat4 and tsc22d1 as novel candidate genes for spontaneous pulmonary adenomas.
Document Type
Article
Publication Date
2011
Keywords
Age-Factors, Aging, Animals, Cadherins, Genetic-Loci, Genome-Wide-Association-Study, Lung-Neoplasms, Mice-Inbred-Strains, Repressor-Proteins, Severity-of-Illness-Index
JAX Source
Cancer Res 2011; 71(17):5779-91.
First Page
5779
Last Page
5791
Abstract
Genetic influences that underlie spontaneous lung oncogenesis are poorly understood. The objective of this study was to determine the genetic influences on spontaneous pulmonary adenoma frequency and severity in 28 strains of mice as part of a large-scale aging study conducted at the Jackson Aging Center (http://agingmice.jax.org/). Genome-wide association studies were conducted in these strains with both low-density (132,000) and high-density (4,000,000) panel of single-nucleotide polymorphisms (SNP). Our analysis revealed that adenomas were relatively less frequent and less severe in females than males, and that loci implicated in frequency and severity were often different between male and female mice. While some of the significant loci identified mapped to genomic locations known to be responsible for carcinogen-induced cancers (e.g., Pas1), others were unique to our study. In particular, Fat4 was influential in males and Tsc22d1 was influential in females. SNPs implicated were predicted to alter amino acid sequence and change protein function. In summary, our results suggested that genetic influences that underlie pulmonary adenoma frequency are dependent on gender, and that Fat4 and Tsc22d1 are likely candidate genes to influence formation of spontaneous pulmonary adenoma in aging male and female mice, respectively.
Recommended Citation
Berndt A,
Cario CL,
Silva KA,
Kennedy VE,
Harrison DE,
Paigen B,
Sundberg JP.
Identification of fat4 and tsc22d1 as novel candidate genes for spontaneous pulmonary adenomas. Cancer Res 2011; 71(17):5779-91.