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Loss of NF1 alleles in phaeochromocytomas from patients with type 1 neurofibromatosis
Author(s) -
Xu W.,
Mulligan L. M.,
Ponder M. A.,
Liu L.,
Ponder B. A. J.,
Smith B. A.,
Mathew C. G. P.
Publication year - 1992
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870040411
Subject(s) - neurofibromatosis , allele , locus (genetics) , biology , neurofibromin 1 , neural crest , genotype , genetics , neurofibromatosis type i , tumor suppressor gene , gene , phenotype , cancer research , carcinogenesis
Type 1 neurofibromatosis (NF1) is a common autosomal dominant disorder that affects tissues derived from the neural crest. The manifestations are varied, comprising generalised disorders of growth and development as well as an increased risk of benign and malignant tumours including phaeochromocytomas and neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11–12, and recently the NF1 gene has been cloned. Deletions identified in the constitutional genotype of some patients have suggested that the NF1 phenotype may arise from loss of function mutations of the NF1 gene, consistent with the hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1 tumours has not revealed the frequent allele losses encompassing the NF1 locus, implying loss of the wild‐type NF1 allele, which would support this hypothesis. We report allele losses with markers flanking the NF1 region in each of 7 NF1 phaeochromocytomas. In each of the 3 tumours for which this could be determined, the loss involved the wild‐type chromosome. These results provide strong evidence that, in cells of the adrenal medulla at least, the NF1 gene may act as a tumour suppressor.