Molecular characterization of chromosome 22 deletions in schwannomas

Abstract Schwannomas are tumors of the cranial, spinal, and peripheral nerve sheaths that originate from Schwann cells. Acoustic neurinomas are the most frequent cranial schwannomas. They might develop sporadically or in the context of neurofibromatosis type 2 (NF2). Loss of part or all of chromosome 22 is frequently found in acoustic schwannomas, suggesting that the NF2 gene is a tumor suppressor gene involved in the genesis of these tumors. Only a few spinal schwannomas have been molecularly characterized so far, showing that chromosome 22 loss might also occur in these tumors. Here we present the molecular analysis of chromosome 22 in 23 acoustic schwannomas and nine schwannomas of other locations (including other cranial nerves and spinal and peripheral nerves). Most of these tumors were from sporadic cases. Multiple schwannomas of various locations were analyzed in two patients with NF2. We found partial or complete monosomy for chromosome 22 in 22% of the acoustic schwannomas and 55% of the non‐acoustic schwannomas. The tumors with partial monosomy included four with terminal deletions and one with a deletion of the centromeric part of the long arm of chromosome 22. The region between the βB2‐1 crystallin locus (CRYB2A) and the myoglobin locus (MB) was commonly deleted in these tumors. Our studies suggest that a schwannoma‐related tumor suppressor gene within this region, which might be the NF2 gene, is involved in the development of schwannomas of various locations in the nervous system. Our studies indicate that the second hit in the genesis of different schwannomas within one (predisposed) NF2 patient occurs independently and via different mechanisms.