The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis

Xing, Xin; Cai, Weibin; Shi, Huijuan; Wang, Y; Li, M; Jiao, J; Chen, M

doi:10.1038/bjc.2013.251

Cited by 97 publications

(86 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In rectal cancer, Kohonen-Corish et al observed that CDKN2A methlytion occurred in 20% of patients, and that CDKN2A methlytion was associated with poor overall survival (13). CDKN2A hypermethylation is also associated with lymphovascular invasion, lymph node metastasis and proximal tumor location in colorectal cancer (14). In ovarian cancer, deletion of CDKN2A is also a common event (15).…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

et al. 2016

View full text Add to dashboard Cite

Abstract. The aim of the present study was to identify the candidate target genes of genomic aberrations in esophageal squamous cell carcinoma (ESCC). Array comparative genomic hybridization (CGH) and quantitative polymerase chain reaction were applied to analyze the copy number changes and expression level of candidate genes, respectively. Integrative analysis revealed that homozygous deletions of cyclin-dependent kinase inhibitor (CDKN) 2A and CDKN2B and gains of fascin actin-bundling protein 1 (FSCN1) and homer scaffolding protein 3 (HOMER3) occurred frequently in ESCC. The results demonstrated that the homozygous deletion of CDKN2A or CDKN2B was significantly associated with lymph node metastasis. Notably, the expression of CDKN2A and CDKN2B was lower in dysplasia than in normal esophageal epithelium. We also observed that the copy number increase of FSCN1 was significantly associated with pT, pN and pStage, and that the gain of HOMER3 was significantly linked with pN and pStage. We further revealed that FSCN1 and HOMER3 were overexpressed in ESCC, and that their overexpression was correlated with copy number increase. In conclusion, CDKN2A, CDKN2B, FSCN1 and HOMER3 are candidate cancer-associated genes and may play a tumorigenic role in ESCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Alterations in the cell-cycle pathway have been described in multiple cancers (8)(9)(10)(11)(12) and are associated with poorer clinical outcome in some tumor types (13)(14)(15), including acute lymphoblastic leukemia (9), ovarian (10), colon cancer (12), and medulloblastoma (11).…”

Section: Introductionmentioning

confidence: 99%

Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics

Helsten

Kato

Schwaederlé

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Alterations in the cyclin-dependent kinase (CDK)-retinoblastoma (RB) machinery disrupt cell-cycle regulation and are being targeted in drug development. To understand the cancer types impacted by this pathway, we analyzed frequency of abnormalities in key cell-cycle genes across 4,864 tumors using nextgeneration sequencing (182 or 236 genes; Clinical Laboratory Improvement Amendments laboratory). Aberrations in the cellcycle pathway were identified in 39% of cancers, making this pathway one of the most commonly altered in cancer.

show abstract

“…Furthermore, CDKN2A promoter hypermethylation was shown to correlate with poor patient overall survival. 33 In juvenile myelomonocytic leukaemia (JMML), hypermethylation of CDKN2A was observed in 35% of the patients and correlated with poor outcome, 34 similarly to the patients diagnosed with non-small cell lung cancer Review Cancer Stem Cells (NSCLC), hypermethylation of p16 promoter was also associated with worse outcome. 35 The notion of slowing down the replication of cancer cells, a major hallmark of tumour biology, has been of great interest, and the efforts have escalated tremendously with the conceptualisation and discovery of cancer stem cells (CSCs).…”

Section: Polycomb Group Genes and Self-renewalmentioning

confidence: 99%

mentioning

confidence: 99%

Bmi1 – A Path to Targeting Cancer Stem Cells

Bakhshinyan¹,

Adile²,

Venugopal³

et al. 2017

European Oncology &Amp; Haematology

View full text Add to dashboard Cite

T he Polycomb group (PcG) genes encode for proteins comprising two multiprotein complexes, Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2 (PRC2). Although the initial discovery of PcG genes was made in Drosophila, as transcriptional repressors of homeotic (HOX) genes. Polycomb repressive complexes have been since implicated in regulating a wide range of cellular processes, including differentiation and self-renewal in normal and cancer stem cells. Bmi1, a subunit of PRC1, has been long implicated in driving self-renewal, the key property of stem cells. Subsequent studies showing upregulation of Bmi1 in several cancers correlated with increased aggressiveness, radioresistance and metastatic potential, provided rationale for development of targeted therapies against Bmi1. Although Bmi1 activity can be reduced through transcriptional, post-transcriptional and post-translational regulation, to date, the most promising approach has been through small molecule inhibitors targeting Bmi1 activity. The post-translational targeting of Bmi1 in colorectal carcinoma, lung adenocarcinoma, multiple myeloma and medulloblastoma have led to significant reduction of self-renewal capacity of cancer stem cells, leading to slower tumour progression and reduced extent of metastatic spread. Further value of Bmi1 targeting in cancer can be established through trials evaluating the combinatorial effect of Bmi1 inhibition with current 'gold standard' therapies. KeywordsPolycomb group (PcG) genes, Bmi1, Mel-18, cancer stem cells (CSCs), self-renewal Disclosure: David Bakhshinyan, Ashley A Adile, Chitra Venugopal and Sheila K Singh have nothing to disclose in relation to this article.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Compliance with Ethics:This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. 1 PRC2 initiates gene silencing through the activity of histone deacetylase (HDAC), and histone methyltransferases that can methylate lysine 9 and 27 residues on histone H3 and lysine 26 on histone H1.2-6 The stable gene repression is then maintained by PRC1 through recognition of tri-methylated H3K27 (H3K27me3).3 The canonical repression pathway is initiated through trimethylation of H3K27 on the promoter of target gene by PRC2 subunit EZH1 or its paralog EZH2.2-4 The H3K27me3 mark is readily recognised by PRC1 through chromatin binding ability of its subunit CBX. The repression is further maintained through ubiquitination of lysine 119 residue on histone H2A (H2AK119ub) by RING1, a subunit of PRC1, or chromatin condensation. [7][8][9] Promoters of the polycomb target genes have been generally characterised as CpG-rich DNA sequences that are lacking other epigenetic markers.10-14 However, several other models of context depen...

show abstract

The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis

Cited by 97 publications

References 28 publications

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

Cell-Cycle Gene Alterations in 4,864 Tumors Analyzed by Next-Generation Sequencing: Implications for Targeted Therapeutics

Bmi1 – A Path to Targeting Cancer Stem Cells

Contact Info

Product

Resources

About