Overrepresentation of chromosome 12p sequences and karyotypic evolution in i(12p)-negative testicular germ-cell tumors revealed by fluorescence in situ hybridization

Suijkerbuijk, Ron F.; Sinke, Richard J.; Meloni, Aurelia M.; Parrington, Jennifer M.; Echten, Jannie van; Jong, Bauke M. de; Oosterhuis, J. Wolter; Sandberg, Avery A.; Kessel, Ad Geurts van

doi:10.1016/0165-4608(93)90173-j

Cited by 89 publications

(39 citation statements)

References 30 publications

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“…In spite of the characteristic pattern of gains and losses, the only obligatory change found in TGCTs is overrepresentation of the short arm of chromosome 12, associated in over 80% of these tumors with the presence of one or more isochromosomes 12p (i(12p)) (Mostert et al, 1998;Roelofs et al, 2000 for review). Moreover, extra copies of sequences from the short arm of chromosome 12 has been demonstrated in TGCTs without i(12p) (Rodriguez et al, 1993;Suijkerbuijk et al, 1993). These ®ndings demonstrate that the short arm of chromosome 12 contains relevant genes of which an additional copy number is crucial for the development of this cancer.…”

Section: Introductionmentioning

confidence: 77%

Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas

Gurp²,

et al. 2000

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Overrepresentation of 12p-sequences, mostly due to isochromosome formation, is the only consistent chromosomal alteration found in invasive testicular germ cell tumors of adolescents and young adults (TGCTs), both seminomas and the various histological elements of nonseminomas. The biological role of extra 12p in the pathogenesis of this cancer is unclear, and it is also unknown so far, whether it is an early event, i.e., already present in carcinoma in situ, or related to invasive growth. Using comparative genomic hybridization (CGH) with DOP-PCR ampli®ed DNA isolated from micro-dissected tumor cells, and double¯uorescent in situ hybridization (FISH) on frozen tissue sections, we investigated the presence of overrepresentation of 12p sequences in di erent development stages of four seminomas and seven nonseminomas, in total 17 invasive components, in addition to the carcinoma in situ of each. CGH demonstrated relative gain of 12p-sequences in all invasive components except one, con®rmed by FISH in most samples. In contrast, no gain was found in the carcinoma in situ samples by any of the methods. These ®ndings show that overrepresentation of 12p is not an early event in the development of TGCTs, but relates to invasive growth. Oncogene (2000) 19, 5858 ± 5862.

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Section: Introductionmentioning

confidence: 77%

Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas

Gurp²,

et al. 2000

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“…It has been known for more than a decade that the majority of TGCTs contains one or more isochromosomes of the short arm of chromosome 12 (Mukherjee et al, 1991;Rodriquez et al, 1993a;Van Echten et al, 1995;Mostert et al, 1996b). Moreover, it has been demonstrated, that TGCTs without i(12p) also show over-representation of 12p-sequences (Suijkerbuijk et al, 1993;Rodriquez et al, 1993b;Smolarek et al, 1995). Since in those studies a paint for the whole short arm of chromosome 12 was used, or a probe which was not mapped in detail, it was not possible to localize the region involved.…”

Section: Discussionmentioning

confidence: 99%

“…In the majority of TGCTs tested this was due to the presence of one or more copies of isochromosome 12p [i(12p)]. In addition, it was found using¯uorescence in situ hybridization (FISH) that TGCTs without i(12p) always show overrepresentation of 12p-sequences cryptically hidden in the genome (Suijkerbuijk et al, 1993;Rodriquez et al, 1993b;Smolarek et al, 1995). We showed that i(12p) may also be present in CIS (Vos et al, 1990), indicating that over-representation of 12p-sequences is probably a relatively early event in the pathogenesis of this cancer, not related to invasive growth.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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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 identi®cation of the relevant gene(s) were based on thè 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 ampli®cations 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 ampli®cations 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 ampli®cation (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 identi®cation of the gene(s) involved in TGCT-development.

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“…This is because of an isochromosome 12p in 80% of cases (reviewed by Sandberg et al, 1996). In approximately 10% of primary TGCTs, amplification in the 12p11.2-p12.1 region has been reported (Suijkerbuijk et al, 1993;Mostert et al, 1996;Korn et al, 1996;Rao et al, 1998;Summersgill et al, 1998a;Roelofs et al, 2000). This has been predominantly found in seminomas although it has been seen in nonseminomas but in a more heterogeneous cellular pattern.…”

Section: Introductionmentioning

confidence: 95%

Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1

et al. 2003

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Gain of 12p material is invariably associated with testicular germ cell tumors (TGCTs) of adolescents and adults, most usually as an isochromosome 12p. We analyzed TGCTs with i(12p) using a global approach to expression profiling targeting chromosomes (comparative expressed sequence hybridization, CESH). This indicated overexpression of genes from 12p11.2-p12.1 relative to testis tissue and fibroblasts. The nonseminoma subtype showed higher levels of expression than seminomas. Notably, 12p11.2-p12.1 is amplified in about 10% of TGCTs and CESH analysis of such amplicon cases showed high levels of overexpression from this region. Microarray analysis, including cDNA clones representing most UniGene clusters from 12p11.2-p12.1, was applied to DNA and RNA from 5 TGCTs with amplification of 12p11.2-p12.1 and seven TGCTs with gain of the entire short arm of chromosome 12. Expression profiles were consistent with the CESH data and overexpression of EST595078, MRPS35 and LDHB at 12p11.2-p12.1 was detected in most TGCTs. High-level overexpression of BCAT1 was specific to nonseminomas and overexpression of genes such as CMAS, EKI1, KRAS2, SURB7 and various ESTs correlated with their amplification. Genes such as CCND2, GLU3, LRP6 and HPH1 at 12p13 were also overexpressed. The overexpressed sequences identified, particularly those in the region amplified, represent candidate genes for involvement in TGCT development.

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Overrepresentation of chromosome 12p sequences and karyotypic evolution in i(12p)-negative testicular germ-cell tumors revealed by fluorescence in situ hybridization

Cited by 89 publications

References 30 publications

Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas

Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas

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

Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2–p12.1

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