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Publication : Identification of fat4 and tsc22d1 as novel candidate genes for spontaneous pulmonary adenomas.

First Author  Berndt A Year  2011
Journal  Cancer Res Volume  71
Issue  17 Pages  5779-91
PubMed ID  21764761 Mgi Jnum  J:175528
Mgi Id  MGI:5285990 Doi  10.1158/0008-5472.CAN-11-1418
Citation  Berndt A, et al. (2011) Identification of fat4 and tsc22d1 as novel candidate genes for spontaneous pulmonary adenomas. Cancer Res 71(17):5779-91
abstractText  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.
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