High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays

Impact of copy number on gene expression

Maija Wolf, Spyro Mousses, Sampsa Hautaniemi, Ritva Karhu, Pia Huusko, Minna Allinen, Abdel Elkahloun, Outi Monni, Yidong Chen, Anne Kallioniemi, Olli Kallioniemi (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

106 Citations (Scopus)

Abstract

Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13% and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses), at 3q, 5p, 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.
Original languageEnglish
Pages (from-to)240 - 247
Number of pages8
JournalNeoplasia
Volume6
Issue number3
DOIs
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed

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Comparative Genomic Hybridization
Gene Dosage
Oligonucleotide Array Sequence Analysis
Prostatic Neoplasms
Gene Expression
Gene Rearrangement
Loss of Heterozygosity
Telomere
Microarray Analysis
Genes
Genome
Cell Line
Neoplasms

Keywords

  • Copy number alteration
  • prostate cancer
  • gene expression
  • cDNA microarray
  • CGH microarray

Cite this

Wolf, Maija ; Mousses, Spyro ; Hautaniemi, Sampsa ; Karhu, Ritva ; Huusko, Pia ; Allinen, Minna ; Elkahloun, Abdel ; Monni, Outi ; Chen, Yidong ; Kallioniemi, Anne ; Kallioniemi, Olli. / High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays : Impact of copy number on gene expression. In: Neoplasia. 2004 ; Vol. 6, No. 3. pp. 240 - 247.
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abstract = "Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13{\%} and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses), at 3q, 5p, 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.",
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Wolf, M, Mousses, S, Hautaniemi, S, Karhu, R, Huusko, P, Allinen, M, Elkahloun, A, Monni, O, Chen, Y, Kallioniemi, A & Kallioniemi, O 2004, 'High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays: Impact of copy number on gene expression', Neoplasia, vol. 6, no. 3, pp. 240 - 247. https://doi.org/10.1593/neo.3439

High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays : Impact of copy number on gene expression. / Wolf, Maija; Mousses, Spyro; Hautaniemi, Sampsa; Karhu, Ritva; Huusko, Pia; Allinen, Minna; Elkahloun, Abdel; Monni, Outi; Chen, Yidong; Kallioniemi, Anne; Kallioniemi, Olli (Corresponding Author).

In: Neoplasia, Vol. 6, No. 3, 2004, p. 240 - 247.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays

T2 - Impact of copy number on gene expression

AU - Wolf, Maija

AU - Mousses, Spyro

AU - Hautaniemi, Sampsa

AU - Karhu, Ritva

AU - Huusko, Pia

AU - Allinen, Minna

AU - Elkahloun, Abdel

AU - Monni, Outi

AU - Chen, Yidong

AU - Kallioniemi, Anne

AU - Kallioniemi, Olli

PY - 2004

Y1 - 2004

N2 - Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13% and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses), at 3q, 5p, 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.

AB - Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13% and gains at iq and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, 17q (losses), at 3q, 5p, 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, corresponding to common deletions and gains of often large chromosomal regions.

KW - Copy number alteration

KW - prostate cancer

KW - gene expression

KW - cDNA microarray

KW - CGH microarray

U2 - 10.1593/neo.3439

DO - 10.1593/neo.3439

M3 - Article

VL - 6

SP - 240

EP - 247

JO - Neoplasia

JF - Neoplasia

SN - 1522-8002

IS - 3

ER -