Meningioma: a cytogenetic model of a complex benign human tumor, includingdata on 394 karyotyped cases

Meningioma is the most frequent tumor of neuroectodermal origin in humans. It is usually benign. Only a minority of cases shows progression to an anap lastic tumor (WHO grade II and III). Meningioma is generally a sporadic tum or. Multiple and familial cases are rare and mostly associated with (heredi tary) neurofibromatosis 2 (NF2). Meningiomas show an unexpectedly high recu rrence rate. Also, completely removed low-grade tumors can recur. Recurrenc e and multiplicity are correlated with the formation of a peritumoral edema . On the cytogenetic level, meningioma is the best-studied tumor in humans. Grade I tumors show either uniform monosomy 22 or a diploid karyotype. The majority of high-grade, but only a minority of low-grade, meningiomas show loss of merlin, a cytoskeleton-cytoplasm-linker protein. Merlin is the pro duct of the NF2 gene located on chromosome 22. A second tumor suppressor ge ne on chromosome 22 has not yet been detected. In contrast to other solid t umors, progression of meningiomas is correlated with increasing hypodiploid y, showing characteristic clonal evolutions that mostly include chromosomes 14, 18, and 19 and, more rarely, 6 and 10. Structural aberrations are infr equent, except for the loss of the short arm of chromosome 1, which appears to be the decisive step for anaplastic growth. Comparative histochemical a nd molecular cytogenetic studies point to the alkaline phosphatase gene (AL PL, liver-bone-kidney type) located on I p36.1 --> p34 as a candidate tumor suppressor gene. A model is proposed that tries to explain - with a minimu m number of essential steps - the origin, progression, infiltration, and re currence of meningiomas. Copyright (C) 2001 S. Karger AG, Basel.