Loss of Heterozygosity at 1p, 7q, 17p, and 22q in Meningiomas

Abstract

Objective : Allelic losses or loss of heterozygosity (LOH) at many chromosomal loci have been found in the cells of meningiomas. The objective of this study was to evaluate LOH at several loci of different chromosomes (1p32, 17p13, 7q21, 7q31, and 22q13) in different grades of meningiomas. Methods : Forty surgical specimens were obtained and classified as benign, atypical, and anaplastic meningiomas. After DNA extraction, ten polymorphic microsatellite markers were used to detect LOH. Medical and surgical records, as well as pathologic findings, were reviewed retrospectively. Results : LOH at 1p32 was detected in 24%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. Whereas LOH at 7q21 was found in only one atypical meningioma. LOH at 7q31 was found in one benign meningioma and one atypical meningioma. LOH at 17p13 was detected in 4%, 40%, and 80% in benign, atypical, and anaplastic meningiomas, respectively. LOH at 22q13 was seen in 48%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. LOH results at 1p32 and 17p13 showed statistically significant differences between benign and non-benign meningiomas. Conclusion : LOH at 1p32 and 17p13 showed a strong correlation with tumor progression. On the other hand, LOH at 7q21 and 7q31 may not contribute to the development of the meningiomas. KEY WORDS :Chromosome˙ Loss of heterozygosity˙ Meningiomas.

Masked hypodiploidy in anaplastic meningiomas by duplication of the original clone found in atypical meningiomas: Illustration of the evolution of genetic alterations

“…25 In addition, the frequency of 1p/14q increases with increasing tumor grade with anaplastic meningiomas showing up to 100% deletion of 1p and up to 60% deletion of 14q. 15,22,23,26 Similarly, the 2005 atypical meningioma of the present case, showed both deletions of 1p and 14q and recurred twice with malignant progression to anaplastic grade I and grade II.…”

“…Meningiomas with codeletion of 1p and 14q are more likely to recur up to 75% in WHO grade I tumors and up to 100% in WHO grade II and III, whereas only 4.3% of meningiomas recur when 1p is intact . In addition, the frequency of 1p/14q increases with increasing tumor grade with anaplastic meningiomas showing up to 100% deletion of 1p and up to 60% deletion of 14q . Similarly, the 2005 atypical meningioma of the present case, showed both deletions of 1p and 14q and recurred twice with malignant progression to anaplastic grade I and grade II.…”

“…Deletions have been found in meningiomas in the following chromosomes: 1p, 3q, 6q, 10q, 17p, 18p, 18q and 22q . Of these, 22q13 is the most common, and is found in 40–100% of meningiomas, followed by chromosome 1p . NF2 is a tumor suppressor gene on 22q and has been linked with the development of benign meningiomas .…”

“…12 Of these, 22q13 is the most common, and is found in 40-100% of meningiomas, 13,14 followed by chromosome 1p. 15,16 NF2 is a tumor suppressor gene on 22q and has been linked with the development of benign meningiomas. 17 Based on the fact that the majority of sporadic meningiomas and meningiomas of all grades possess the 22q deletion, Weber et al 18 report that the deletion of 22q is the initial event for meningioma formation and pathogenesis, whereas progression, based on a-CGH of 62 sporadic meningiomas, is related to deletions in 1p and 14q (Weber).The 22q deletion is found in up to 60% of atypical meningiomas and up to 100% of anaplastic meningiomas.…”

The correlation of clinical and chromosomal alterations of benign meningiomas and their recurrences

“…Finally at least a quarter of patients harbouring a benign MG experience a tumor relapse within 20 years [14]. Therefore, some prognosis-related factors have been proposed to identify a clinically aggressive subset of benign MGs: familial occurrence, patient age, tumor location, Ki-67/MIB-1 labelling index, telomerase activity, proliferating cell nuclear antigen [15][16][17]. Recently the molecular biology has attempted to explain the recurrence phenomena of a completely removed MG [10,[18][19][20].The milestone was the identification of the NF2 gene on the long arm of chromosome 22 (22q12.2) that is responsible for the production of merlin (a cytoskeletal protein).…”