Reference SummaryBerndt A, Cancer Res 2011 Sep 1;71(17):5779-91

Title

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

Authors

Berndt A; Cario CL; Silva KA; Kennedy VE; Harrison DE; Paigen B; Sundberg JP

Journal

Cancer Res

Volume

71

Issue

17

Year

2011

Pages

5779-91

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. Cancer Res; 71(17); 5779-91. (c)2011 AACR.

Links

21764761 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
129S1/SvImJ Lung adenoma Lung

15.38 - 33.33

A/J Lung adenoma Lung

28.57 - 66.67

BALB/cByJ Lung adenoma Lung

13.33 - 33.33

BTBR T+ Itpr3tf/J Lung adenoma Lung

0 - 50

BUB/BnJ Lung adenoma Lung

0

C3H/HeJ Lung adenoma Lung

0

C57BL/10J Lung adenoma Lung

0

C57BL/6J Lung adenoma Lung

0 - 7.14

C57BLKS/J Lung adenoma Lung

0

C57BR/cdJ Lung adenoma Lung

0 - 13.33

C57L/J Lung adenoma Lung

6.67 - 14.29

CBA/J Lung adenoma Lung

7.69 - 9.09

DBA/2J Lung adenoma Lung

0

FVB/NJ Lung adenoma Lung

16.67 - 28.57

KK/HlJ Lung adenoma Lung

0

LP/J Lung adenoma Lung

23.08 - 28.57

MRL/MpJ Lung adenoma Lung

0

NOD/ShiLtJ Lung adenoma Lung

0 - 11.11

NON/ShiLtJ Lung adenoma Lung

7.69 - 16.67

NZO/HlLtJ Lung adenoma Lung

33.33 - 40

NZW/LacJ Lung adenoma Lung

0

P/J Lung adenoma Lung

0

PL/J Lung adenoma Lung

0 - 50

PWD/PhJ Lung adenoma Lung

7.69 - 10

RIIIS/J Lung adenoma Lung

25 - 28.57

SM/J Lung adenoma Lung

18.18 - 23.08

SWR/J Lung adenoma Lung

28.57 - 40

WSB/EiJ Lung adenoma Lung

9.09