Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex genetic alterations in cervical cancer

Kloth, Judith; Oosting, Jan; Wezel, Tom van; Szuhai, Károly; Knijnenburg, Jeroen; Gorter, Arko; Kenter, Gemma G.; Fleuren, Gert Jan; Jordanova, Ekaterina S.

doi:10.1186/1471-2164-8-53

Cited by 68 publications

(45 citation statements)

References 61 publications

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“…Nevertheless, a rather poor correlation has been found between amplification and gene expression in this region, both in cell lines (22%) [16] and invasive tumors (18.9%) [22]. Although in the present study, a higher percentage of genes was deregulated (33.5%), a large proportion of the investigated genes was not deregulated.…”

Section: Discussioncontrasting

confidence: 80%

“…In cell lines having 5p amplified, only 22% of the investigated genes were upregulated. Similarly, invasive tumors or cell lines having amplified 3q showed even a lower proportion of upregulated genes [16]. The lack of correlation between copy number (CN) and gene expression [16], [31] suggests that some of the altered regions identified by SNP or mCGH arrays could be CN-altered discontinuously and not all genes within the regions are affected.…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, invasive tumors or cell lines having amplified 3q showed even a lower proportion of upregulated genes [16]. The lack of correlation between copy number (CN) and gene expression [16], [31] suggests that some of the altered regions identified by SNP or mCGH arrays could be CN-altered discontinuously and not all genes within the regions are affected. However, the role of copy number in gene deregulation has not been studied in detail genome-wide and only particular regions have been investigated [16], [31], [33].…”

Section: Introductionmentioning

confidence: 99%

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Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

et al. 2012

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Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments.

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Section: Discussioncontrasting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

et al. 2012

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“…The results from the aCGH illustrated that the chromosomal instability in tumors is more complicated than a simple deletion, duplication or translocation. This phenomenon of alternating multiple segmental deletions has been reported in other types of solid tumors [13-15]. The same is true for the deletions on chromosome 8q (8q24.12-qter) and 17p (17pter-p12) detected in our study as opposed to the duplications reported by Sowery et al We proceeded with a mutation assay of the TP53 gene located on chromosome 17p.…”

Section: Discussionsupporting

confidence: 87%

Molecular cytogenetic characterization of undifferentiated embryonal sarcoma of the liver: a case report and literature review

Chen

Jin

et al. 2012

Mol Cytogenet

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Undifferentiated embryonal sarcoma of the liver (UESL) represents a heterogeneous group of tumors derived from mesenchymal tissues. Earlier cytogenetic studies in limited cases demonstrated that UESL is associated with a recurrent translocation t(11;19)(q11;q13.3-q13.4) or add(19)(q13.4). In this report, we present our array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH) findings, and a missense mutation of TP53 gene by DNA sequencing in a 19-year-old patient with UESL. The data were compared to laboratory findings reported by previous studies.

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“…One study has found that SRC-3 levels are not differently expressed in healthy cervical tissue and cervical cancer, but SRC-3 expression has been correlated with lymph node involvement [74]. Moreover, the 20q12 genomic region encoding SRC-3 has been found to be amplified in cervical cancer cell lines, however, this would not correlate with an increase in SRC-3 mRNA expression [75]. …”

Section: Cervixmentioning

confidence: 99%

Steroid receptor coactivators as therapeutic targets in the female reproductive system

Szwarc

Lydon

O’Malley

2015

The Journal of Steroid Biochemistry and Molecular Biology

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The Steroid Receptor Coactivators (SRCs/p160/NCOA) are a family of three transcriptional coregulators initially discovered to transactivate the transcriptional potency of steroid hormone receptors. Even though SRCs were also found to modulate the activity of multiple other transcription factors, their function is still strongly associated with regulation of steroid hormone action and many studies have found that they are critical for the regulation of reproductive biology. In the case of the female reproductive tract, SRCs have been found to play crucial roles in its physiology, ranging from ovulation, implantation, to parturition. Not surprisingly, SRCs’ action has been linked to numerous abnormalities and debilitating disorders of female reproductive tissues, including infertility, cancer, and endometriosis. Many of these pathologies are still in critical need of therapeutic intervention and “proof-of-principle” studies have found that SRCs are excellent targets in pathological states. Therefore, small molecule modulators of SRCs’ activity could be applied in the future in the treatment of many diseases of the female reproductive system.

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Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex genetic alterations in cervical cancer

Cited by 68 publications

References 61 publications

Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines

Molecular cytogenetic characterization of undifferentiated embryonal sarcoma of the liver: a case report and literature review

Steroid receptor coactivators as therapeutic targets in the female reproductive system

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