Inherited Mutations in PTEN That Are Associated with Breast Cancer, Cowden Disease, and Juvenile Polyposis
| Autor: | Hanlee P. Ji, Bjørn Tore Gjertsen, Stener Kvinnsland, Eric D. Lynch, Pål Møller, Ketil Heimdal, Elizabeth A. Ostermeyer, Patrick MacLeod, Karen Swisshelm, Mary Claire King, David Suchard, Herb Lubs, J. Fernando Arena, Ming K. Lee, Jamie L. Dann |
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| Rok vydání: | 1997 |
| Předmět: |
Male
PTEN DNA Mutational Analysis Loss of Heterozygosity Breast cancer 0302 clinical medicine Tensin Cowden disease Genes Tumor Suppressor Genetics(clinical) Juvenile polyposis syndrome RNA Neoplasm Genetics (clinical) Cancer Sequence Deletion 0303 health sciences biology DNA Neoplasm Cowden syndrome Kidney Neoplasms Pedigree 3. Good health Adenomatous Polyposis Coli 030220 oncology & carcinogenesis Uterine Neoplasms Female Carcinoma in Situ Research Article Adenoma Adenomatous polyposis coli Breast Neoplasms 03 medical and health sciences Neoplastic Syndromes Hereditary Genetics medicine Humans Point Mutation RNA Messenger Thyroid Neoplasms Carcinoma Renal Cell 030304 developmental biology Tumor Suppressor Proteins Point mutation PTEN Phosphohydrolase medicine.disease Juvenile polyposis Phosphoric Monoester Hydrolases Carcinoma Intraductal Noninfiltrating Haplotypes biology.protein Cancer research Protein Tyrosine Phosphatases Hamartoma Syndrome Multiple |
| Zdroj: | The American Journal of Human Genetics. 61:1254-1260 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/301639 |
| Popis: | SummaryPTEN, a protein tyrosine phosphatase with homology to tensin, is a tumor-suppressor gene on chromosome 10q23. Somatic mutations in PTEN occur in multiple tumors, most markedly glioblastomas. Germ-line mutations in PTEN are responsible for Cowden disease (CD), a rare autosomal dominant multiple-hamartoma syndrome. PTEN was sequenced from constitutional DNA from 25 families. Germ-line PTEN mutations were detected in all of five families with both breast cancer and CD, in one family with juvenile polyposis syndrome, and in one of four families with breast and thyroid tumors. In this last case, signs of CD were subtle and were diagnosed only in the context of mutation analysis. PTEN mutations were not detected in 13 families at high risk of breast and/or ovarian cancer. No PTEN-coding-sequence polymorphisms were detected in 70 independent chromosomes. Seven PTEN germ-line mutations occurred, five nonsense and two missense mutations, in six of nine PTEN exons. The wild-type PTEN allele was lost from renal, uterine, breast, and thyroid tumors from a single patient. Loss of PTEN expression was an early event, reflected in loss of the wild-type allele in DNA from normal tissue adjacent to the breast and thyroid tumors. In RNA from normal tissues from three families, mutant transcripts appeared unstable. Germ-line PTEN mutations predispose to breast cancer in association with CD, although the signs of CD may be subtle. |
| Databáze: | OpenAIRE |
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