Allelic loss at the tuberous sclerosis 2 locus in spontaneous tumors in the Eker rat

Molecular Carcinogenesis - Tập 14 Số 1 - Trang 28-36 - 1995
Raymond S. Yeung1, Guang‐Hui Xiao2, Jeffrey I. Everitt3, Fang Jin2, Cheryl Lyn Walker4
1Division of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
2Division of Medical Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania
3Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina
4Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas

Tóm tắt

AbstractSomatic events leading to the inactivation of tumor suppressor genes often involve chromosomal alterations that can be detected as loss of heterozygosity(a). In the Eker rat, spontaneous tumors of the kidney, uterus, and spleen develop as a result of a germline mutation of the tuberous sclerosis 2(Tsc2) gene. We examined the pattern and frequency of LOH at the predisposing locus in 77 primary tumors and cell lines to gain an understanding of the role of Tsc2 allelic loss in the pathogenesis of Eker‐derived tumors. Although most renal and uterine tumors(primary and cell lines) displayed LOH, splenic hemangiosarcomas did not. Although the presence of normal tissue may account for some of this difference, the possibility exists that an alternative mechanism, such as subtle mutation or gene dosage effects, may be involved during splenic tumorigenesis. Northern analysis confirmed that LOH resulted in loss of the wild‐type transcripts for the Tsc2 gene. Thus, the inactivation of both alleles plays an important role in renal and uterine tumor development, in keeping with Knudson's two‐hit hypothesis. In addition, renal tumors that retained the wild‐type allele also did not express the normal transcript, suggesting that the remaining Tsc2alleles had acquired subtle mutations resulting in loss of gene function.© 1995 Wiley‐Liss, Inc

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Tài liệu tham khảo

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Molecular Carcinogenesis

Tập 14 Số 1

28-36

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