ArticleJapanese journal of cancer research : Gann1997
Intragenic Tsc2 somatic mutations as Knudson's second hit in spontaneous and chemically induced renal carcinomas in the Eker rat model.
Article in Japanese journal of cancer research : Gann, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 56 citations in OpenAlex.
- Tuberous sclerosis complex: a complex case.Cold Spring Harbor molecular case studies · 2022Article
- A population-based study to estimate survival and standardized mortality of tuberous sclerosis complex (TSC) in Taiwan.Orphanet journal of rare diseases · 2021Article
- Choosing The Right Animal Model for Renal Cancer Research.Translational oncology · 2020Review
- Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation-associated renal tumors in Eker rats.Cancer science · 2020Article
- The Neurodevelopmental Pathogenesis of Tuberous Sclerosis Complex (TSC).Frontiers in neuroanatomy · 2020Review
- Endocrine disruptor exposure during development increases incidence of uterine fibroids by altering DNA repair in myometrial stem cells.Biology of reproduction · 2018Article
- Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex.Cancer science · 2017Review
- Suppression of tumor suppressor Tsc2 and DNA repair glycosylase Nth1 during spontaneous liver tumorigenesis in Long-Evans Cinnamon rats.Molecular and cellular biochemistry · 2010Article
- Animal models of lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC).Lymphatic research and biology · 2010Review
- Age dependence of radiation-induced renal cell carcinomas in an Eker rat model.Cancer science · 2010Article
- Genetics and molecular biology of tuberous sclerosis complex.Current genomics · 2008Article
- Renal carcinogenesis: genotype, phenotype and dramatype.Cancer science · 2003Review
- Polycystic kidney disease as a result of loss of the tuberous sclerosis 2 tumor suppressor gene during development.The American journal of pathology · 2003Article
- A novel "Nihon" rat model of a Mendelian dominantly inherited renal cell carcinoma.Japanese journal of cancer research : Gann · 2000Article
- Complete inactivation of the TSC2 gene leads to formation of hamartomas.American journal of human genetics · 1999Article
- Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes.Japanese journal of cancer research : Gann · 1998Article
- Identification of a leader exon and a core promoter for the rat tuberous sclerosis 2 (Tsc2) gene and structural comparison with the human homolog.Mammalian genome : official journal of the International Mammalian Genome Society · 1997Article
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
We searched for the rat homologue of the human tuberous sclerosis (TSC2) gene mutations in loss of heterozygosity (LOH)-negative Eker rat renal carcinomas (RCs) by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis using 45 primer sets covering all 41 coding exons and one leader exon including splicing donor/acceptor sites. We have identified intragenic somatic mutations in 7 of 21 spontaneous RCs, including one cell line (33%), and in 3 of 9 (33%) N-ethyl-N-nitrosourea (ENU)-induced LOH-negative RCs. Interestingly, five mutations in the spontaneous RCs were either deletion or duplication (5/7 = 71%). In contrast, all three in ENU-induced RCs were base substitutions (3/3 = 100%), as expected. Thus, a qualitative difference in the second hit might exist between spontaneous and ENU-induced mutations (e.g., deletion or duplication versus point mutation). By a direct cloning approach utilizing the restriction length difference caused by germline insertional mutation or reverse transcriptase-PCR analysis in two applicable cases, we could clearly show the presence of intragenic somatic mutations in the second copy (wild-type) of the Tsc2 gene. This is the first demonstration at the DNA sequence level of the validity of Knudson's two-hits hypothesis in the Tsc2 gene.
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