Detection of Germlike and Somatic Mutations in the Neurofibromatosis 1 Gene.
Final rept. 22 Sep 93-21 Sep 96,
UTAH UNIV SALT LAKE CITY
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This research project sought to improve mutation detection in the neurofibromatosis 1 gene NF1, to determine the spectrum and significance of germline NF1 mutations in neurofibromatosis 1 patients, and to determine the spectrum and significance of somatic NF1 mutations in sporadic tumors of several types in the general population. Several mutation detection approaches were explored. The best results came from screening the entire Open Reading Frame of the NF1 messenger RNA by two rapid, sensitive as says for changes in length, and one additional assay for mutations that prematurely terminate translation of the neurofibromin protein the combination of these methods resulted in detection of mutations in 19 of 23 unrelated NF1 patients 83. Since these as says systematically miss mutations in mRNA that result only in amino acid substitutions, it is likely that over 90 of neurofibromatosis 1 - causing mutations alter the structure of the NF1 mRNA. No differences in the nature or location of NF1 mutations were discerned when familial and new mutation patients with neurofibromatosis 1 were compared. Somatic NF1 mutations were sought in tumor cell lines established from cancers of the colon, breast, and brain. One or more cell lines representing each tumor type were positive for mutation.
- Anatomy and Physiology
- Medicine and Medical Research