Characterization of chromosomal abnormalities in prostate cancer cell lines by spectral karyotyping

Pan, Yi; Kytölä, Soili; Farnebo, Filip; Wang, N.; Lui, Weng‐Onn; Nupponen, Nina N.; Isola, Jorma; Visakorpi, Tapio; Bergerheim, Ulf S.R.; Larsson, Catharina

doi:10.1159/000015432

Cited by 55 publications

(56 citation statements)

References 25 publications

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“…35 PC3, DU145 and LNCaP have also been studied by SKY. 36 Xenograft DNAs show a perfect match between chromosome 6 alterations as found by CGH and allelotyping, with the exception of PC339. Concomitant loss of 6q and gain of 6p (PC135, PC329) might indicate isochromosome 6p.…”

Section: Search For Homozygous Deletionsmentioning

confidence: 77%

Deletion of chromosomal region 6q14‐16 in prostate cancer

Verhagen

Hermans

Brok

et al. 2002

Intl Journal of Cancer

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A detailed analysis of chromosome 6 in DNAs from prostate cancers was performed, to define a region for subsequent search for cancer genes. DNA from 4 prostate cancer cell lines and 11 xenografts was used for CGH and wholechromosome allelotyping with polymorphic microsatellite markers. Loss of proximal 6q was studied in more detail by high-density allelotyping of xenografts, cell lines and 19 prostate tumour specimens from TURP. Seven of 15 xenografts and cell lines showed deletion of proximal 6q by CGH. Gain of 6q was found in 2 samples. Six samples showed 6p gain, and 1 had 6p loss. Allelotyping results were consistent with CGH data in 11 of 15 DNAs. In LNCaP and DU145 cells, CGH showed 6p loss and 6q loss, respectively, but 2 allelic bands were detected for many polymorphic markers on these chromosome arms. These apparent discrepancies might be explained by aneuploidy. In cell line TSU, allelotyping demonstrated chromosome 6 deletion, which was not clearly detected by CGH, indicating loss of 1 copy of chromosome 6 followed by gain of the retained copy during progressive tumour growth. Loss of heterozygosity was detected in 9 of 19 TURP specimens. Combining all data, we found a common minimal region of loss at 6q14-16 with a length of 8.6 Mbp flanked by markers D6S1609 and D6S417. One hundred and twenty-three STSs, ESTs, genes and candidate genes mapping in this interval were used to screen xenografts and cell lines for HDs, but none was detected. In summary, chromosome region 6q14-16 was deleted in approximately 50% of the prostate cancer specimens analysed. The high percentage of loss underscores the importance of genes within this region in prostate cancer growth.

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Section: Search For Homozygous Deletionsmentioning

confidence: 77%

Deletion of chromosomal region 6q14‐16 in prostate cancer

Verhagen

Hermans

Brok

et al. 2002

Intl Journal of Cancer

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“…No common chromosomal rearrangement or translocation breakpoint was identified. 24,25 In contrast to these highly anaplastic cell lines, earlystage prostatic tumors are typically diploid with some propensity to progress to aneuploidy and karyotypic complexity in advanced stages. 26 The karyotype of PCa1-met is comparable to the latter, with surprisingly few chromosomal alterations produced by as few as six breakpoints involving chromosomes 4, 6, 12, 13, 22 and Y.…”

Section: Discussionmentioning

confidence: 99%

An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line

Wang

Xue

Cutz

et al. 2005

Laboratory Investigation

105

110

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Metastasis is the major cause of prostate cancer deaths and there is a need for clinically relevant in vivo models allowing elucidation of molecular and cellular mechanisms underlying metastatic behavior. Here we describe the development of a new in vivo model system for metastatic prostate cancer. Pieces of prostate cancer tissue from a patient were grafted in testosterone-supplemented male NOD-SCID mice at the subrenal capsule graft site permitting high tumor take rates. After five serial transplantations, the tumor tissues were grafted into mouse prostates. Resulting tumors and suspected metastatic lesions were subjected to histopathological and immunohistochemical analysis. Samples of metastatic tissue were regrafted in mouse anterior prostates and their growth and spread examined, leading to isolation from lymph nodes of a metastatic subline, PCa1-met. Orthotopic grafting of PCa1-met tissue in 47 hosts led in all cases to metastases to multiple organs (lymph nodes, lung, liver, kidney, spleen and, notably, bone). Histopathological analysis showed strong similarity between orthotopic grafts and their metastases. The latter were of human origin as indicated by immunostaining using antibodies against human mitochondria, androgen receptor, prostate-specific antigen and Ki-67. Spectral karyotyping showed few chromosomal alterations in the PCa1-met subline. This study indicates that transplantable subrenal capsule xenografts of human prostate cancer tissue in NOD-SCID mice can, as distinct from primary cancer tissue, be successfully grown in the orthotopic site. Orthotopic xenografts of the transplantable tumor lines and metastatic sublines can be used for studying various aspects of metastatic prostate cancer, including metastasis to bone.

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“…In addition, the aCGH data of the cell lines were highly concordant with previously published cCGH and spectral karyotypic (SKY) and/or multicolor FISH (M-FISH) data. 17,18,20,21 Unfortunately, most of the cell lines do not contain typical chromosomal alterations of clinical prostate tumors. In this respect, the LuCaP xenografts, analyzed here, resemble clinical tumors more closely.…”

Section: Minimal Amplified Regions Defined By Van Duin Et Almentioning

confidence: 99%

Genetic aberrations in prostate cancer by microarray analysis

Saramäki

Porkka

Vessella

et al. 2006

Intl Journal of Cancer

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The aim of this study was to screen genetic as well as expression alterations in prostate cancer. Array comparative genomic hybridization (aCGH) to a 16K cDNA microarray was performed to analyze DNA sequence copy number alterations in 5 prostate cancer cell lines and 13 xenografts. The aCGH confirmed the previously implicated common gains and losses, such as gains at 1q, 7, 8q, 16p and 17q and losses at 2q, 4p/q, 6q, 8p, 13q, 16q, 17p and 18q, which have previously been identified by chromosomal CGH (cCGH). Because of the higher resolution of aCGH, the minimal commonly altered regions were significantly narrowed-down. For example, the gain of 8q was mapped to three independent regions, 8q13.3-q21.11, 8q22.2 and 8q24.13-q24.3. In addition, a novel recurrent gain at 9p13-q21 was identified. The concomitant expression analysis indicated that genome-wide DNA sequence copy number (gene dosage) was significantly associated with the expression level (p < 0.0001). The analyses indicated several individual genes whose expression was associated with the gene copy number. For example, gains of PTK2 and FZD6, were associated with the increased expression, whereas losses of TNFRSF10B (alias DR5) and ITGA4 with decreased expression. In conclusion, the aCGH mapping data will aid in the identification of genes altered in prostate cancer. The combined expression and copy number analysis suggested that even a low-level copy number change may have significant effect on gene expression, and thus on the development of prostate cancer. ' 2006 Wiley-Liss, Inc.Key words: prostatic carcinoma; neoplasia; amplification; deletion; expression; cDNA microarray; molecular cytogenetics Genetic alterations underlying the development and progression of prostate cancer are incompletely known. Chromosomal comparative genomic hybridization (cCGH) as well as analysis of loss of heterozygosity (LOH) have been used to screen prostate tumors for chromosomal aberrations. Several chromosomal regions have been implicated in these studies (reviewed in Ref. 1). The chromosomal arms containing losses most often are 6q, 8p, 10q, 13q, 16q and 18q, whereas the most common gains are found in chromosomes 7, 8q and Xq. The losses at 6q, 8p and 13q seem to be early events, found also in prostate intraepithelial neoplasia (PIN). On the other hand, the gains of chromosome 7 and 8q are late events and are associated with aggressive phenotype. The gain of Xq is found especially in hormone-refractory prostate carcinomas. The actual genes affected in these chromosomal regions are often not known. Moreover, only a few genes that are commonly altered, either genetically or epigenetically, in prostate cancer have been identified (reviewed in Ref. 1).Microarray technologies are now commonly being used for expression analysis of large numbers of genes. Several studies, using either oligo or cDNA microarrays, on expression profiling in prostate cancer have already been published (reviewed in Ref. 2). These have indicated that a number of genes, such as EZH2, 3 AMACR4 hepsin, ...

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Characterization of chromosomal abnormalities in prostate cancer cell lines by spectral karyotyping

Cited by 55 publications

References 25 publications

Deletion of chromosomal region 6q14‐16 in prostate cancer

Deletion of chromosomal region 6q14‐16 in prostate cancer

An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line

Genetic aberrations in prostate cancer by microarray analysis

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