Article
Comprehensive FISH analysis reveals gains of chromosome 22q12.1 and 22q13.3 in cytogenetically non-aberrant meningiomas
Gewinne der chromosomalen Regionen 22q12.1 und 22q13.3 in zytogenetisch unauffälligen Meningeomen mittels FISH-Analyse
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Published: | April 23, 2004 |
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Outline
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Objective
Loss of chromosome 22 is a characteristic cytogenetic finding in 50% of sporadic meningiomas. At chromosome 22 the loss of neurofibromatosis 2/merlin (NF2) tumor suppressor is held responsible for meningioma development although only about 60% of the meningiomas have loss of NF2 function. Therefore we wanted to know what is characteristic for the remaining 40% of meningiomas concerning chromosome 22. Is there another chromosomal region on chromosome 22 which is important for meningioma development?
Methods
We analyzed 16 meningiomas by conventional cytogenetic study: 8 showed no chromosomal aberrations concerning chromosome 22 and 8 revealed a loss of chromosome 22 (with or without further chromosomal aberrations). We investigated primary meningioma cell cultures and smear preparations of meningioma by fluorescence in situ hybridization (FISH) with probes for the following regions: 22q11.2, 22q11.23q12.1, 22q12.1 and 22q13.3.
Results
For all analyzed meningiomas with loss of chromosome 22 in cytogenetic analysis we confirmed these cytogenetic data by interphase FISH. Microdeletions of parts of chromosome 22 could be detected in 6/8 non-aberrant meningiomas as loss of the proximal or of the distal signals in 9-28% of nuclei per case. Interestingly, in 2/8 cytogenetic inconspicuous meningiomas we found gains of the 22q13.3 region and in 2/8 cases gains of 22q12.1 region. One case showed no aberrations concerning chromosome 22 by FISH.
Conclusions
Our data suggest a new hypothesis for meningioma progression: first a region of 22q12.1 and 22q13.3 might be gained and translocated on different chromosomes. As a second event, these regions will be deleted on one chromosome 22 which results in interphase FISH in disomy and is only visible as a translocation phenomenon in metaphase FISH. A further shortening of the partial deleted chromosome 22 might result in the well-known complete loss of chromosome 22.