Title: 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH
Authors: Zafarana, Gaetano ×
Grygalewicz, Beata
Gillis, Ad J M
Vissers, Lisenka E L M
van de Vliet, Walter
van Gurp, Ruud J H L M
Stoop, Hans
Debiec-Rychter, Maria
Oosterhuis, Jan Wolter
van Kessel, Ad Geurts
Schoenmakers, Eric F P M
Looijenga, Leendert H J
Veltman, Joris A #
Issue Date: Oct-2003
Series Title: Oncogene. vol:22 issue:48 pages:7695-701
Abstract: All invasive testicular germ cell tumors of adolescents and adults (TGCTs), that is, seminomas and nonseminomas, show gain of 12p sequences, mostly as isochromosomes. Although several candidate genes have been suggested, the relevant gene(s) have not been identified yet. About 10% of testicular seminomas, however, show a more restricted amplification of the 12p11.2-p12.1 region, in which the various amplicons show an apparent overlap, allowing for the shortest region of amplification overlap approach, aiming at the identification of pathogenetically relevant sequences residing in this region. Here we report on a high-resolution 12p-amplicon architecture analysis using microarray-based comparative genomic hybridization, the results of which were subsequently confirmed by fluorescent in situ hybridization studies. The 12p-specific microarray contained 63 positionally selected BAC clones, which are more or less evenly distributed over the short arm of chromosome 12 (average spacing: less than 500 Kb), including 20 clones within the region of amplification. Out of a series of 17 seminomas, seven seminomas showed amplification of the whole amplicon region, of which three showed a dip in T/R value in the center of the amplified area. A more complex amplification pattern was found in the other 10 seminomas: three showed predominant amplification at the centromeric border; one mainly at the telomeric border; six showed a balanced amplification of both the centromeric and telomeric regions. The only nonseminoma investigated showed a structure in which the centromeric border was only amplified. These data support a mechanistic model in which at least two 12p genes, situated at the border regions of the amplicon, are positional candidates capable of actively supporting tumor progression in TGCTs.
ISSN: 0950-9232
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Genetics Section (-)
Laboratory for Genetics of Malignant Disorders
× corresponding author
# (joint) last author

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