The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis.

摘要: Schwannomatosis is characterized by the predisposition to develop multiple schwannomas and, less commonly, meningiomas. Despite clinical overlap with neurofibromatosis type 2 (NF2), schwannomatosis not caused germline NF2 gene mutations. Instead, mutations of either SMARCB1 or LZTR1 tumour suppressor genes have been identified in 86% familial and 40% sporadic patients. In contrast patients rhabdoid tumours, which are due complete loss-of-function mutations, individuals harbour predominantly hypomorphic give rise synthesis mutant proteins residual function that do cause tumours. Although biallelic detected tumours schwannomatosis, classical two-hit model tumorigenesis insufficient account for schwannoma growth, since also frequently inactivated these Consequently, must involve mutation at least two different genes, an occurrence mediated loss heterozygosity large parts chromosome 22q harbouring only but NF2. Thus, paradigmatic a syndrome concomitant mutational inactivation more genes. This review provides overview current models patterns underlying will ultimately help explain complex presentation this rare disease.