Molecular Identification of the Schwannomatosis Locus
Annual rept. 1 Jul 2003-30 Jun 2004
MASSACHUSETTS GENERAL HOSPITAL BOSTON
Pagination or Media Count:
Schwannomatosis is a recently recognized third major type of neurofibromatosis. Our preliminary studies of the NF2 gene in tumors from schwannomatosis patients reveal a pattern of tumor suppressor gene inactivation not previously reported in any other human disease. The objective of this project is to clone the locus responsible for familial schwannomatosis. We are exploring two competing hypotheses which address both the non random distribution of LOH observed in schwannomatosis tumors and the high rate of somatic NF2 mutation seen along the cis allele. Specific Aims 1 To identify and clinically characterize schwannomatosis patients, and maintain a resource of tumor and blood specimens. 2 To further refine the candidate region on chromosome 22 using linkage and loss of heterozygosity analyses. 3 To determine the molecular mechanism of tumor formation in these patients using complementary molecular and cytogenetic approaches. Schwannomatosis patients and affected relatives will be identified. Blood and tumor specimens will be obtained for linkage, LOH, FISH and mutational analysis of coding and non coding candidate regions. Relevance This study will elucidate the unique pathogenesis of schwannomatosis and provide a means for definitive diagnosis using molecular technology.
- Medicine and Medical Research