Abstract 324: Classic and molecular cytogenetic characterization of adult malignant gliomas
Authors: Pecciarini Lorenza , Vicentini Caterina , Talarico Anna , Martino Davide Di , Cin Elena Dal , Terreni Maria Rosa , Cunsolo Crocifissa Lo , Cangi Maria Giulia , Doglioni Claudio 
Published: June 2012

Over the past years there has been an increasing use of molecular markers in the evaluation of adult malignant gliomas, as chromosome 1p/19q codeletion, O-6 methylguanine-DNA methyltransferase (MGMT) gene promoter methylation, and epidermal growth factor receptor (EGFR) gene amplification. However treatment challenges posed by malignant gliomas remain considerable, many of those deriving from their complex and still unclear molecular heterogeneity.

In order to shed further light into genetic aberrations characterizing human malignant gliomas we performed classical and molecular cytogenetic analysis on 35 CNS tumors (21 glioblastoma, 6 astrocitoma, 4 oligodendroglioma, 2 mixed neuroglial tumors, 1 oligoastrocitoma, 1 gliosarcoma). Metaphases were obtained in 25 cases for which conventional karyotyping was carried on by Q-banding: 22 cases showed complex karyotypes, with both numerical and structural chromosomal abnormalities. For 5 cases, M-FISH analysis was performed allowing better definition of such aberrations. EGFR gene copy number was studied by FISH in 27 cases and 5 of them (18,5%) showed EGFR amplification. MGMT gene promoter methylation was analysed by MS-PCR in 17 gliomas and methylation was observed in 9 cases (53%).

1p/19q FISH analysis showed codeletion in 1 oligodendroglioma, 1p deletion in 1 oligodendroglioma and 1 glioblastoma and 19q deletion in 1 astrocitoma and 1 glioblastoma.

In oligodendrogliomas 1p/19q codeletion is caused by the unbalanced translocation t(1;19)(q10;p10) and 1p/19q loss has been validated as both prognostic marker and predictive of radio-chemosensitivity. It is important to distinguish 1p/19q codeletion from 1p partial distal deletions, typically involving 1p36 region. Indeed, 1p36 partial deletions occur in astrocytic tumors and are associated with a poor prognosis; in fact they have not yet been extensively investigated, and no specific gene mapping to this deleted region has been identified so far.

We identified two balanced translocations [t(1;7)(p36;q22); t(1;15)(p36;p21)] in 2 different astrocitomas and 1p36 deletion and 1p36 inversion [inv(1)(p36.2;q42)] in the same glioblastoma. Interestingly, these translocations may represent the first of the two events needed to inactivate a tumor suppressor gene; a second event, such as 1p36 deletion, could lead to the astrocitoma progression to glioblastoma. In particular the glioblastoma carrying both 1p36 deletion and inversion may represent the index case for searching the gene targeted by these alterations. Remarkably, as several chromosome 1p studies in gliomas have been conducted on archival materials by FISH, the real involvement of 1p36 in specific aberrations, such as translocations, may have been underestimated. Further investigation is needed to better characterize 1p36 aberrations in gliomas, and to identify genes involved in these aberrations and potentially related to disease progression.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 324. doi:10.1158/1538-7445.AM2011-324