Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human

@article{EwartToland2003IdentificationOS,
  title={Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human},
  author={Amanda Ewart-Toland and Paraskevi Briassouli and John P. de Koning and Jian-Hua Mao and Jinwei Yuan and Florence Chan and Lucy MacCarthy-Morrogh and Bruce A. J. Ponder and Hiroki Nagase and John Burn and Sarah W. Ball and Maria Almeida and Spiros Linardopoulos and Allan Balmain},
  journal={Nature Genetics},
  year={2003},
  volume={34},
  pages={403-412}
}
Linkage analysis and haplotype mapping in interspecific mouse crosses (Mus musculus × Mus spretus) identified the gene encoding Aurora2 (Stk6 in mouse and STK15 in human) as a candidate skin tumor susceptibility gene. The Stk6 allele inherited from the susceptible M. musculus parent was overexpressed in normal cells and preferentially amplified in tumor cells from F1 hybrid mice. We identified a common genetic variant in STK15 (resulting in the amino acid substitution F31I) that is… 
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References

SHOWING 1-10 OF 43 REFERENCES
Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers
TLDR
The positional cloning of the mouse gene Scc1 (Susceptibility to colon cancer 1) and the identification of Ptprj, encoding a receptor-type protein tyrosine phosphatase, as the underlying gene are reported and suggest that PTPRJ is relevant to the development of several different human cancers.
Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.
We report here the molecular cloning of an approximately 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of
The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64
TLDR
It is demonstrated that the Mom1AKR allele consists of two genetic components, which include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines and a second region, distal to Pla 2g 2a, which has also been identified using fine structure recombinants.
A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines
TLDR
In isolation of a novel gene named BTAK, encoding a putative member of protein serine/threonine kinase family localized on chromosome 20q13 that is amplified and overexpressed in breast tumor cell lines, the findings suggest that amplification and overeexpression of BTAk may be playing a critical role in oncogenic transformation of breast tumor cells.
Complex interactions of new quantitative trait loci, Sluc1, Sluc2, Sluc3, and Sluc4, that influence the susceptibility to lung cancer in the mouse
TLDR
QTL analysis of 222 F2 mice revealed four new loci that influence susceptibility to lung cancer (Sluc genes), indicating that interactions between tumour susceptibility genes are a common phenomenon which complicates their mapping.
A subset of skin tumor modifier loci determines survival time of tumor-bearing mice.
TLDR
Analysis of skin tumor susceptibility in interspecific Mus musculus/Mus spretus hybrid mice suggests that host genetic factors may be used to predict carcinoma growth rate and/or survival of individual backcross mice exposed to the same carcinogenic stimulus and suggests that mouse models may provide an approach to the identification of genetic modifiers of cancer survival in humans.
Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer.
  • M. Tanner, S. Grénman, J. Isola
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 2000
TLDR
The high frequency of gene amplification at chromosomal region 20q12-q13 suggests that the genes amplified therein may play a central role in the pathogenesis of sporadic and hereditary ovarian carcinoma.
A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers
TLDR
It is demonstrated that the Aurora2 gene maps to chromosome 20q13, a region amplified in a variety of human cancers, including a significant number of colorectal malignancies, which implicate aurora2 as a potential oncogene in many colon, breast and other solid tumors, and identify centrosome‐associated proteins as novel targets for cancer therapy.
Allelotype analysis of mouse skin tumors using polymorphic microsatellites: sequential genetic alterations on chromosomes 6, 7, and 11.
TLDR
The first attempt to allelotype a nonhuman tumor, i.e., chemically induced mouse skin tumors, using a panel of polymorphic microsatellite markers indicated that markers on chromosomes 6 and 7 were imbalanced, consistent with trisomy in both benign and malignant skin tumors.
...
...