Constitutional DNA‐level aberrations in chromosome 22 in a patient with multiple meningiomas

Abstract

We describe a patient who developed multiple meningiomas but had no clear evidence of neurofibromatosis type 2. Four of the tumors, derived from three different sites, were analyzed cytogenetically and/or at the DNA level using chromosome 22 specific probes. All four tumors showed loss of the same copy of chromosome 22. On the chromosome that was retained in the tumors, we found two constitutional aberrations, a 1.5 kb deletion and a point mutation. The patient had inherited both alterations from her father. The father has not developed any meningiomas so far but he has been treated for a well-differentiated adenocarcinoma of the lung and a brain metastasis from this tumor. The mother and 75 unrelated individuals did not show any of the chromosome 22 alterations. The multiple tumors found in the patient suggest that she has a predisposing gene for the development of meningiomas. The finding that all investigated tumors lost the same, constitutionally normal copy of chromosome 22 could indicate that the predisposing gene resides on chromosome 22 and was affected by the constitutional mutations.

Molecular genetics of meningiomas

“…73 This discrepancy between the higher incidence of chromosome 22 LOH and the lower frequency of NF2 gene mutations has led to the search for a second tumor suppressor gene on 22q, in proximity to but distinct from the NF2 gene. 2,20,26,43,44,68,72,73,78 These studies have resulted in other possible candidates, including the BAM22, LARGE, MN1, and INI1 genes ( Table 2 and Fig. 4).…”

Pathophysiology of Meningiomas

“…Several researchers have suggested the likelihood of a second tumor suppressor gene on the q arm of chromosome 22, in close proximity to but distinct from the NF2 gene. 23,[44][45][46][47][48][49][50][51] Next to chromosome 22 anomalies, deletion of the short arm of chromosome 1 is the most frequent alteration detected by cytogenetic analysis of meningiomas. 52 Loss of chromosome 1p has been shown to correlate with meningioma progression, with FISH studies showing monosomy 1p in 70% of atypical and almost 100% of anaplastic meningiomas.…”