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Genome-wide analysis of genomic imbalances in intracranial
ependymomas
Piergiorgio Modena, Joris Weltman, Elena Lualdi, Federica Facchinetti,
Irene Janssen, Lisenka Wissers, Felice Giangaspero, Marco Forni, Gaetano
Finocchiaro, Riccardo Riccardi, Franca Fossati Bellani, Maura Massimino, Eric
Schoenmakers, Gabriella Sozzi
Istituto Nazionale per lo Studio e la Cura dei
Tumori, Milano, Italy, Microarray Facility - University Medical Center,
Nijmegen, Netherlands, Ospedale A. Gemelli, Roma, Italy, Ospedale Infantile
Regina Margherita, Torino, Italy, Istituto Neurologico C.Besta, Milano, Italy.
E-mail: piergiorgio.modena@istitutotumori.mi.it
Ependymoma is a rare glial neoplasm that accounts for approximately 10% of brain
tumors in childhood.
This tumor is frequent in young children, and half of the
cases occur before age 5.
In contrast to adult ependymomas, that are located
mostly in the spinal cord and display frequent NF2 mutations, pediatric
ependymomas are 90% intracranial and do not display NF2 mutations.
The most
frequently rearranged chromosomal regions identified by either cytogenetic or
molecular approaches are 1q, 6q, 16, 17p, 22q.
The chromosomal region 22q is the
most frequently lost in intracranial cases, but the involvement of known tumor
suppressors located in 22q has been already investigated and excluded.
So far,
few molecular studies have analyzed the genetic alterations of intracranial
ependymomas, and were unable to refine sufficiently the chromosomal regions
rearranged in order to identify the genes involved.
Diagnosis and treatment of
the Italian patients follows uniform criteria established by a national
protocol, providing a homogeneous sample of patients informative for correlation
between genetic alterations and clinical parameters.
Our aim is to analyse
retrospectically and prospectically the Italian cases by microarray-based
Comparative Genomic Hybridization (array-CGH), and preliminary results obtained
so far will be presented.
We analysed 22 paediatric intracranial ependymoma
cases by array-CGH at 1 Mb resolution.
This technique allows the detection of
genomic imbalances at higher resolution compared to traditional CGH by
substituting chromosome preparations with well-defined genomic DNA fragments
arrayed on glass slides, as hybridization targets.
We detected frequent regions
of loss on chromosomes 6q, 9, 16q, 17p, 22 and regions of gain on chromosomes
1q, 11q, 7 and 20.
We confirmed array-CGH results by either loss of
heterozigosity or interphase-FISH analyses.
Several tumors showed evidence of
genetic heterogeneity by array-CGH analysis, and this phenomenon was clearly
confirmed by FISH experiments, demonstrating the high sensitivity of array-CGH
procedure.
Investigation of the minimally involved chromosomal regions and of
association between genetic profiles and clinical parameters will be presented.
Copyright © 2004 American Association for Cancer Research. All rights
reserved.
Source: http://aacr04.agora.com/planner/displayabstract.asp?presentationid=4650
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