Comparative genomic hybridization analysis of genomic alterations in benign,atypical and anaplastic meningiomas

BACKGROUND: Meningiomas are common tumors of the central nervous system. Although most are benign tumors, approximately 10% show a histologic progression to a higher malignancy grade similar to atypical (GII) and anaplastic (GIII) meningiomas. Monosomy 22q12 is the most frequent genetic alteration detected in these tumors, but failure of detection of 22q mutations in about 40% of tumors which are indistinguishable from meningiomas with 22q deletions with respect to clinical and histopathologic features, makes it apparent that an alternative mechanism is responsible for the initiation of meningioma. Moreover, little is known about genetic alterations during malignant progression of meningioma. PURPOSE: In order to determine the genetic pathways underlying the development of meningioma, 15 benign (WHO grade I), 7 atypical (WHO grade II) and 3 anaplastic (WHO grade III), sporadic meningiomas were screened by Comparative Genomic Hybridization (CGH). RESULTS: Statistical analysis revealed a significant correlation between the number of chromosomal imbalances and the tumor grade; the numbers of total alterations detected per tumor were 2.20 (2.24 for GI, 10.00 (1.17 for GII and 14.66 (1.15 for GIII. The most frequent abnormality seen in benign tumors was loss on 22q (47%). The second alteration was 1p deletion (33%) and this abnormality was also the common aberration in three tumors without CGH detected 22q deletion. In GII, aberrations most commonly identified were losses on 1p (6/7 cases), 22q (5/7 cases), 10q (4/7 cases), 14q and 18q (3/7 cases) as well as gains on 15q and 17q (3/7 cases). In GIII, genomic loss on 1p was the most commonly observed abnormality (3/3). Losses on 9p, 10q, 14q, 15q, 18q and 22q as well as gains on 12q, 15q and 18p were the other genomic alterations detected by CGH. Combined 1p/14q deletions were encountered in 2/15 benign, 3/7 atypical and 2/3 anaplastic meningiomas. By CGH, DNA sequences on 17q21-qter were seen to be amplified in 1/7 GII and 2/3 GIII, whereas highly amplified DNA sequences on 12q13-qter, 20q and 22q11-q12 were seen in one GII, two GII/one GIII, and one GIII, respectively. CONCLUSION: It was concluded that chromosomal deletion from 1p could play a major role in the initiation and progression of meningiomas and that 1p/14q deletions could be a primary focus of further detailed assessment of tumour genesis.