Análise de alterações no número de cópias envolvendo os cromossomos 1p e 22 em meningiomas de baixo grau

Abstract

Meningiomas are the second most common type of primary brain tumor, originating in the meninges covering the brain and spinal cord. They show slow growth, and are found more often in the CNS, being benign in most case, although there are also cases of meningiomas classified as malignant. At the cytogenetic level, meningiomas are the most well studied tumors in humans: studies in CNS tumors have shown that most cases had chromosomal abnormalities, and the most common alterations in theis type of tumor are the loss of one copy of chromosome 22 and deletion of the short arm of chromosome 1. These alterations have been associated with the tumorigenesis process, because they are found mostly in low-grade tumors, particularly deletions involving chromosome 22. Thus, the aim of this study was to analyze the occurrence of copy number alterations (CNAs) involving chromosomes 1p and 22 meningiomas grade I and II, and in addition to verifying the existence of other recurrent rearrangements through the application of high resolution comparative genomic hybridization (array - CGH ). Tumor samples were collected from eight patients. All samples showed gains and losses of various chromosomal segments. Except for one case, all others showed, in different degrees though, more deletions than amplifications. Loss of 1p segments was observed in all samples. Some CNAs were recurrent, being found up to six out of the eight cases. Pair 22 showed CNV in all samples, but the total monosomy was observed in only two of the eight samples. The global analysis of CNAs in all samples showed that, although changes 1p and 22 were the most frequent observed alterations, as expected, other genomic regions had also alterations in various samples, indicating a possible involvement of these modifications in the process of tumorigenesis and tumor progression. For instance, alterations in pairs 9, 12 and 17, have been observed in other studies and were correlated with atypical and anaplastic meningiomas. Our data indicate the existence of a larger number of genomic alterations in low-grade meningiomas, disagreeing partly with the assumption that these tumors are characterized by a small number of changes, usually involving pair 22 and, less frquently, loss of 1p. However, the fact that these tumors present alterations that are classically found in meningiomas, even benign, such as deletions in 1p and 22q, may be an indication that these changes must be linked with the early events of origin in meningiomas, as already suggested several times by other authors . In conclusion, these alterations remain important markers in meningiomas, and the relationships of these and other CNAs with the response to different treatments and recurrences should be the next step after cytogenomic characterization based on array-CGH has been completed.