TY - JOUR
T1 - 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH
AU - Zafarana, Gaetano
AU - Grygalewicz, Beata
AU - Gillis, Ad J M
AU - Vissers, Lisenka E L M
AU - van de Vliet, Walter
AU - van Gurp, Ruud J H L M
AU - Stoop, Hans
AU - Debiec-Rychter, Maria
AU - Oosterhuis, Jan Wolter
AU - van Kessel, Ad Geurts
AU - Schoenmakers, Eric F P M
AU - Looijenga, Leendert H J
AU - Veltman, Joris A
N1 - Funding Information:
This work was financially supported by the Dutch Cancer Society (DDHK 98-1685), Interuniversity Poles of attraction program of Belgium, and the EC COST-B19 action ‘Molecular cytogenetics of solid tumors’ (BG).
PY - 2003/10/23
Y1 - 2003/10/23
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aging/genetics
KW - Chromosome Aberrations
KW - Chromosomes, Artificial, Bacterial/genetics
KW - Chromosomes, Human, Pair 12/genetics
KW - Gene Amplification/genetics
KW - Humans
KW - In Situ Hybridization, Fluorescence
KW - Male
KW - Neoplasms, Germ Cell and Embryonal/genetics
KW - Nucleic Acid Hybridization
KW - Oligonucleotide Array Sequence Analysis
KW - Testicular Neoplasms/genetics
UR - http://www.scopus.com/inward/record.url?scp=0345304237&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1207011
DO - 10.1038/sj.onc.1207011
M3 - Article
C2 - 14576833
SN - 0950-9232
VL - 22
SP - 7695
EP - 7701
JO - Oncogene
JF - Oncogene
IS - 48
ER -