Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes

Rolf Skotheim, Reija Autio, Guro E. Lind, Sigrid M. Kraggerud, Peter W. Andrews, Outi Monni, Olli Kallioniemi, Ragnhild A. Lothe

Research output: Contribution to journalArticleScientificpeer-review

69 Citations (Scopus)

Abstract

INTRODUCTION: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified.

MATERIALS AND METHODS: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH), and integrated the data with transcriptome profiles of the same samples.

RESULTS: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes.

CONCLUSION: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.
Original languageEnglish
Pages (from-to)315-326
JournalCellular oncology
Volume28
Issue number5-6
DOIs
Publication statusPublished - 2006
MoE publication typeA1 Journal article-refereed

Fingerprint

Transcriptome
Genome
Gene Expression
Carcinogenesis
DNA Copy Number Variations
Genes
Suppressor Genes
Embryonal Carcinoma Stem Cells
Triploidy
Glyceraldehyde-3-Phosphate Dehydrogenases
Comparative Genomic Hybridization
Gene Expression Profiling
Karyotype
Oncogenes
Young Adult
Chromosomes
Cell Line
DNA
Testicular Germ Cell Tumor

Keywords

  • Array-CGH
  • comparative genomic hybridization
  • gene expression
  • microarray
  • testicular germ cell tumor

Cite this

Skotheim, R., Autio, R., Lind, G. E., Kraggerud, S. M., Andrews, P. W., Monni, O., ... Lothe, R. A. (2006). Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cellular oncology, 28(5-6), 315-326. https://doi.org/10.1155/2006/219786
Skotheim, Rolf ; Autio, Reija ; Lind, Guro E. ; Kraggerud, Sigrid M. ; Andrews, Peter W. ; Monni, Outi ; Kallioniemi, Olli ; Lothe, Ragnhild A. / Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. In: Cellular oncology. 2006 ; Vol. 28, No. 5-6. pp. 315-326.
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Skotheim, R, Autio, R, Lind, GE, Kraggerud, SM, Andrews, PW, Monni, O, Kallioniemi, O & Lothe, RA 2006, 'Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes', Cellular oncology, vol. 28, no. 5-6, pp. 315-326. https://doi.org/10.1155/2006/219786

Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. / Skotheim, Rolf; Autio, Reija; Lind, Guro E.; Kraggerud, Sigrid M.; Andrews, Peter W.; Monni, Outi; Kallioniemi, Olli; Lothe, Ragnhild A.

In: Cellular oncology, Vol. 28, No. 5-6, 2006, p. 315-326.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes

AU - Skotheim, Rolf

AU - Autio, Reija

AU - Lind, Guro E.

AU - Kraggerud, Sigrid M.

AU - Andrews, Peter W.

AU - Monni, Outi

AU - Kallioniemi, Olli

AU - Lothe, Ragnhild A.

PY - 2006

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N2 - INTRODUCTION: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified.MATERIALS AND METHODS: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH), and integrated the data with transcriptome profiles of the same samples.RESULTS: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes.CONCLUSION: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.

AB - INTRODUCTION: Testicular germ cell tumors of adolescent and young adult men (TGCTs) generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified.MATERIALS AND METHODS: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH), and integrated the data with transcriptome profiles of the same samples.RESULTS: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes.CONCLUSION: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.

KW - Array-CGH

KW - comparative genomic hybridization

KW - gene expression

KW - microarray

KW - testicular germ cell tumor

U2 - 10.1155/2006/219786

DO - 10.1155/2006/219786

M3 - Article

VL - 28

SP - 315

EP - 326

JO - Cellular oncology

JF - Cellular oncology

SN - 2211-3428

IS - 5-6

ER -