Incidence of numerical chromosome aberrations in meningioma tumors as revealed by fluorescence in situ hybridization using 10 chromosome‐specific probes

Abstract

Objective: Although information on the cytogenetic characteristics of meningioma tumors has accumulated progressively over the past few decades, information on the genetic heterogeneity of meningiomas is still scanty. The aim of the present study was to analyze by interphase fluorescence in situ hybridization (FISH) the incidence of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y in a group of 70 consecutive meningioma tumors. Another goal was to establish the potential associations among the altered chromosomes, as a way to assess both intertumoral and intratumoral heterogeneity. Methods: For the purpose of the study, 70 patients diagnosed with meningioma were analyzed. Interphase FISH for the detection of numerical abnormalities for chromosomes 1, 9, 10, 11, 14, 15, 17, 22, X, and Y was applied to fresh tumor samples from each of the patients studied. Results: The overall incidence of numerical abnormalities was 76%. Chromosome Y in males and chromosome 22 in the whole series were the most common abnormalities (46% and 61%, respectively). Despite the finding that monosomy of chromosome 22/22q -deletions are the most frequent individual abnormality (53%), we have observed that chromosome gains are significantly more common than chromosome losses (60% versus 40%). Chromosome gains corresponded to abnormalities of chromosomes 1 (27%), 9 (25%), 10 (23%), 11 (22%), 14 (33%), 15 (22%), 17 (23%), and X in females (35%) and males (23%) whereas chromosome losses apart from chromosome 22 frequently involved chromosomes 14 (19%), X in males (23%), and Y in males (32%). Although an association was found among most gained chromosomes on one side and chromosome losses on the other side, different association patterns were observed. Furthermore, in the latter group, monosomy 22/22q -was associated with monosomy X in females and monosomy 14/14q -was associated with nulisomy Y in males. In addition, chromosome losses usually involved a large proportion of the tumor cells whereas chromosome gains were restricted to small tumor cell clones, including tetraploid cells. Conclusions: Our results show that meningiomas are genetically heterogeneous tumors that display different patterns of numerical chromosome changes, as assessed by interphase FISH. Cytometry (Clin. Cytometry) 50:153-159, 2002.

Fluorescent In Situ Hybridization 1p/19q Deletion/Imbalance Analysis of Low-Grade and Atypical Meningiomas

“…3,6,[13][14][15] The present results showed that MIB-1 labeling index is useful for grading meningiomas, but there is significant overlap. In contrast, FISH analysis of the 1p/19q status clearly distinguished atypical meningioma from low-grade meningioma.…”

“…16) Chromosome 22q deletion and/or mutation of neurofibromatosis type 2 gene (NF2) are most frequently detected as the earliest genetic aberrations and found in meningiomas of all malignancy grades, indicating that inactivation of this gene represents an early event in the pathogenesis of meningiomas. 14,15,19,20) LOH for loci on chromosome 22q and mutations in the NF2 locus probably do not play a role in the development of malignancy in meningiomas. 16) Thus, the assessment of chromosome 22q is not suitable for the alterations associated with progression of meningiomas.…”

“…LOH associated with meningioma progression has been extensively researched, 2,16,18) but only limited data on chromosomal aberrations by FISH are available. 3,6,[13][14][15] FISH analysis should be assessed as numerical genomic abnormalities at the cytogenetic level, not as the rate of chromosome gain or loss. 6,14,15) Assessment of FISH deletion status is useful for the evaluation of chromosomal instability of meningiomas.…”

“…3,6,[13][14][15] FISH analysis should be assessed as numerical genomic abnormalities at the cytogenetic level, not as the rate of chromosome gain or loss. 6,14,15) Assessment of FISH deletion status is useful for the evaluation of chromosomal instability of meningiomas. The frequency of deletions is proportional to histological grade and chromosome 1p deletion was identified in 23% of low-grade and 56% of atypical meningiomas.…”

Comprehensive DNA Copy Number Profiling of Meningioma Using a Chromosome 1 Tiling Path Microarray Identifies Novel Candidate Tumor Suppressor Loci

“…The female-derived tumor M67 displayed a tumor-specific aberration for clones derived from chromosome X, consistent with heterozygous deletion on this chromosome. Deletions on chromosome X have previously been reported for female-derived meningiomas (29,(37)(38)(39). Thus, in tumors shown in Fig.…”