Molecular Basis of Glomus Tumours

Abstract

Glomus tumours of the fingers and toes develop secondarily to the biallelic inactivation of the NF1 gene and are part of the NF1 tumour spectrum. Glomus tumours are small, benign neoplasms that arise from the glomus body, a thermoregulatory shunt commonly found in the fingers and toes. Glomus tumours typically present with at least two of the features of the classic triad of symptoms: severe paroxysmal pain, point tenderness and cold hypersensitivity. Sporadic glomus tumours of fingers and toes are solitary and affect women of middle age. NF1-associated glomus tumours can be multifocal and also demonstrate a female predominance. Treatment is surgical, although tumour or pain recurrence is not uncommon. Pathogenic germline and somatic mutations (or loss of heterozygosity) of NF1 have been reported in nine NF1-associated glomus tumours, including two (22 %) that underwent mitotic recombination of chromosome arm 17q. Consistent with NF1 biallelic inactivation, monoclonal expansion has been documented in glomus tumours. Loss of neurofibromin function in NF1 −/− glomus cells resulted in RAS-MAPK hyperactivation. There is no evidence for NF1 inactivation or overactivation of the RAS-MAPK pathway in glomus cells from sporadic glomus tumours. A variety of copy-number changes, as determined by SNP arrays, have been reported in NF1-associated glomus tumours.