Evaluation of allelic instability in MEN 2A and FMTC tumors
- Bowman Gray School of Medicine, Winston-Salem, NC (United States); and others
Allelic instability of genomic DNA in tumors derived from individuals with multiple endocrine neoplasia type 2A (MEN 2A) or medullary thyroid carcinoma (MTC) was evaluated. Fourteen highly polymorphic dinucleotide repeat polymorphism markers from 5 different chromosomes were tested. Allelic difference between tumor and peripheral blood leukocyte DNA was observed in 4 of 9 tumors, 2 of which showed allelic instability at more than 1 locus. Pet 1, a sporadic, moderately aggressive MTC, revealed allelic instability at 5 different loci from 4 chromosomes. Rut1, an aggressive MTC from a patient with MEN 2A, revealed genetic instability at 3 different loci, all located on chromosome 10. Microsatellite instability has been associated with hereditary nonpolyposis colon cancer (HNPCC) and has been attributed to germline mutations in hMSH2. In MEN 2A and familial MTC, the initiating event in tumorigenesis is a germline mutation in the receptor tyrosine kinase RET. Progression to full tumor development likely required additional somatic mutations. The presence of microsatellite instability in some MTCs suggests that these additional mutations may affect DNA repair genes such as hMSH2 that has been associated with HNPCC.
- OSTI ID:
- 133572
- Report Number(s):
- CONF-941009--
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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