Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92846
Title:
Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults.
Authors:
Mostert, M C; Verkerk, A J; Van de Pol, M; Heighway, Jim; Marynen, P; Rosenberg, C; Van Kessel, A G; Van Echten, J; De Jong, B; Oosterhuis, J W; Looijenga, L H
Abstract:
Cytogenetically, testicular germ cell tumors of adolescents and adults (TGCTs) are characterized by gain of 12p-sequences, most often through isochromosome formation (i(12p)). Fluorescence in situ hybridization (FISH) has shown that i(12p))-negative TGCTs also cryptically contain extra 12p-sequences. The consistency of 12p-over-representation in all histological subtypes of TGCTs, including their preinvasive stage, suggests that gain of one or more genes on 12p is crucial in the development of this cancer. So far, studies aimed at the identification of the relevant gene(s) were based on the 'candidate-gene approach'. No convincing evidence in favor of or against a particular gene has been reported. We combined conventional karyotyping, comparative genomic hybridization, and FISH to identify TGCTs with amplifications of restricted regions of 12p. Out of 49 primary TGCTs (23 without i(12p), 13 with and 13 unknown), eight tumors (six without i(12p) and two unknown) showed amplifications corresponding to 12p11.1-p12.1. Using bicolour-FISH, physical mapping, and semi-quantitative polymerase chain reactions, the size of the shortest region of overlap of amplification (SROA) was estimated to be between 1750-3000 kb. In addition, we mapped a number of genes in and around this region. While fourteen known genes could be excluded as candidates based on their location outside this region, we demonstrate that KRAS2, JAW1 and SOX5 genes are localized within the SROA. While KRAS2 and JAW1 map to the proximal border of the SROA, SOX5 maps centrally in the SROA. KRAS2 and JAW1 are expressed in all TGCTs, whereas one 12p amplicon-positive TGCT lacks expression of SOX5. The critical region of 12p over-represented in TGCTs is less than 8% of the total length of the short arm of chromosome 12. It will be helpful in the identification of the gene(s) involved in TGCT-development.
Affiliation:
Laboratory for Experimental Patho-Oncology, Daniel den Hoed Cancer Center, University Hospital Rotterdam, The Netherlands.
Citation:
Identification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults. 1998, 16 (20):2617-27 Oncogene
Journal:
Oncogene
Issue Date:
May-1998
URI:
http://hdl.handle.net/10541/92846
DOI:
10.1038/sj.onc.1201787
PubMed ID:
9632138
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMostert, M Cen
dc.contributor.authorVerkerk, A Jen
dc.contributor.authorVan de Pol, Men
dc.contributor.authorHeighway, Jimen
dc.contributor.authorMarynen, Pen
dc.contributor.authorRosenberg, Cen
dc.contributor.authorVan Kessel, A Gen
dc.contributor.authorVan Echten, Jen
dc.contributor.authorDe Jong, Ben
dc.contributor.authorOosterhuis, J Wen
dc.contributor.authorLooijenga, L Hen
dc.date.accessioned2010-02-24T12:10:49Z-
dc.date.available2010-02-24T12:10:49Z-
dc.date.issued1998-05-
dc.identifier.citationIdentification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults. 1998, 16 (20):2617-27 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid9632138-
dc.identifier.doi10.1038/sj.onc.1201787-
dc.identifier.urihttp://hdl.handle.net/10541/92846-
dc.description.abstractCytogenetically, testicular germ cell tumors of adolescents and adults (TGCTs) are characterized by gain of 12p-sequences, most often through isochromosome formation (i(12p)). Fluorescence in situ hybridization (FISH) has shown that i(12p))-negative TGCTs also cryptically contain extra 12p-sequences. The consistency of 12p-over-representation in all histological subtypes of TGCTs, including their preinvasive stage, suggests that gain of one or more genes on 12p is crucial in the development of this cancer. So far, studies aimed at the identification of the relevant gene(s) were based on the 'candidate-gene approach'. No convincing evidence in favor of or against a particular gene has been reported. We combined conventional karyotyping, comparative genomic hybridization, and FISH to identify TGCTs with amplifications of restricted regions of 12p. Out of 49 primary TGCTs (23 without i(12p), 13 with and 13 unknown), eight tumors (six without i(12p) and two unknown) showed amplifications corresponding to 12p11.1-p12.1. Using bicolour-FISH, physical mapping, and semi-quantitative polymerase chain reactions, the size of the shortest region of overlap of amplification (SROA) was estimated to be between 1750-3000 kb. In addition, we mapped a number of genes in and around this region. While fourteen known genes could be excluded as candidates based on their location outside this region, we demonstrate that KRAS2, JAW1 and SOX5 genes are localized within the SROA. While KRAS2 and JAW1 map to the proximal border of the SROA, SOX5 maps centrally in the SROA. KRAS2 and JAW1 are expressed in all TGCTs, whereas one 12p amplicon-positive TGCT lacks expression of SOX5. The critical region of 12p over-represented in TGCTs is less than 8% of the total length of the short arm of chromosome 12. It will be helpful in the identification of the gene(s) involved in TGCT-development.en
dc.language.isoenen
dc.subjectTesticular Canceren
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshChromosome Mapping-
dc.subject.meshChromosomes, Human, Pair 12-
dc.subject.meshGene Amplification-
dc.subject.meshGerminoma-
dc.subject.meshHumans-
dc.subject.meshIn Situ Hybridization, Fluorescence-
dc.subject.meshIsochromosomes-
dc.subject.meshKaryotyping-
dc.subject.meshMale-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshTesticular Neoplasms-
dc.titleIdentification of the critical region of 12p over-representation in testicular germ cell tumors of adolescents and adults.en
dc.typeArticleen
dc.contributor.departmentLaboratory for Experimental Patho-Oncology, Daniel den Hoed Cancer Center, University Hospital Rotterdam, The Netherlands.en
dc.identifier.journalOncogeneen

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