Common 9p haplotype in Dutch familial atypical multiple mole-melanoma (FAMMM) syndrome families; no evidence for involvement of MTS1
- Leiden Univ. (Netherlands); and others
A melanoma susceptibility locus was recently located at the short arm of chromosome 9. In the present study linkage analysis was performed in seven Dutch families from the Lieden region with familial atypical multiple mole-melanoma (FAMMM) syndrome with several microsatellite markers from the p21 area of chromosome 9. FAMMM is characterized by the familial occurrence of malignant melanoma of the skin (CMM) in combination with multiple atypical nevi (AN). The relationship between the ultimate phenotype melanoma and the postulated precursors, atypical nevi, is unclear and until now it is uncertain if CMM and AN can be explained by the same gene defect. Marker D9S171 showed the highest two-point lod score of 3.26 at a recombination fraction of 0.01, under an incompletely penetrant, dominant model for melanoma. Combined multipoint linkage analysis in six of the families placed the gene between the markers D9S171 and D9S126 with a maximum lod score of 4.22 at D9S126 and no indication for locus heterogeneity. Interestingly, the occurrence of a common high-risk haplotype in five of the families suggests a unique ancestral mutation in the Leiden region. Our findings provide further evidence that the short arm of chromosome 9 harbors a gene that plays a critical role in predisposition to familial melanoma. However, so far no mutations in the recently identified tumor suppressor gene MTS1 (p16) in the 9p21 region can be found in the Dutch familial melanoma patients.
- OSTI ID:
- 133508
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0236
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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