Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

PloS One
Jesus Perez-LosadaJian-Hua Mao

Abstract

Genome-wide association studies (GWAS) have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs) and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%). There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the pres...Continue Reading

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Citations

Mar 26, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Chuan-Ming XieYi Sun
Aug 11, 2015·Life Sciences in Space Research·Mary Helen Barcellos-HoffMichael M Weil
May 10, 2015·International Journal of Radiation Oncology, Biology, Physics·Elijah F EdmondsonKathryn A Mason
Feb 23, 2019·Cancers·Bethsebie Lalduhsaki SailoAjaikumar Bahulayan Kunnumakkara
Mar 5, 2016·Cold Spring Harbor Protocols·Karlyne M Reilly

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Methods Mentioned

BETA
genotyping
ubiquitination
PCR
electrophoresis

Software Mentioned

ABI Primer Express
SPSS

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