Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype

Auwera, Ilse Van der; Laere, Steven J. Van; Bosch, Sandra M. van den; Eynden, Gert G. Van den; Trinh, B; Dam, Peter van; Colpaert, Cécile; Engeland, Manon van; Marck, Eric A. Van; Vermeulen, Peter B.; Dirix, Luc

doi:10.1038/sj.bjc.6604705

Cited by 64 publications

(49 citation statements)

References 43 publications

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“…For example, APC methylation is associated with inflammation. 40 We do not have information regarding inflammation in these samples. Age may also complicate the results as DNA methylation changes with aging.…”

Section: Discussionmentioning

confidence: 99%

Methylation profiling identified novel differentially methylated markers includingOPCMLandFLRT2in prostate cancer

Davison

et al. 2016

Epigenetics

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To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS 7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (nD70) vs. those without (nD86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3C4 cases and GS 4C3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (nD30) than in the no-recurrence (nD52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa.

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Section: Discussionmentioning

confidence: 99%

Methylation profiling identified novel differentially methylated markers includingOPCMLandFLRT2in prostate cancer

Davison

et al. 2016

Epigenetics

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“…EpiScope ® Methylated HeLa Genomic DNA (Takara Bio) was used as a positive control for methylated alleles. HNOKs genomic DNA was used as a negative control for unmethylated genes (19,33).…”

Section: Methodsmentioning

confidence: 99%

High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer

Koike

Kasamatsu

Iyoda

et al. 2012

International Journal of Oncology

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Abstract.The four and a half LIM domains 1 (FHL1) gene has been related to carcinogenesis. However, the expression status of FHL1 in human oral squamous cell carcinoma (OSCC) remains unclear and the detailed mechanism of gene silencing is poorly understood. The aim of this study was to examine the FHL1 expression level and its regulatory mechanism in OSCCs. Quantitative reverse-transcriptase-polymerase chain reaction (PCR) and western blotting showed significant downregulation of FHL1 in all OSCC-derived cell lines (Sa3, HSC-2, HSC-3, HSC-4, HO-1-u-1, HO-1-N-1, KON and Ca9-22) compared to human normal oral keratinocytes. We also found that FHL1 mRNA expression was frequently downregulated (P<0.01) in 51 (86.4%) of 59 primary OSCCs compared with the corresponding normal oral tissues, while there was no significant difference between the status of the FHL1 protein expression in OSCCs and the clinicopathological features. Using methylationspecific PCR, we detected methylated FHL1 in all cell lines and treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine restored the FHL1 expression. However, no significant restoration of FHL1 expression was observed using sodium butyrate, an inhibitor of histone deacetylase and chromatin immunoprecipitation showed that histone H3 lysine 9 in the FHL1 promoter region was significantly acetylated. In addition, no mutation in the entire coding region of the FHL1 gene was found. Therefore, our data suggested that inactivation of the FHL1 gene is a frequent event during oral carcinogenesis and that the mechanism of FHL1 downregulation in OSCCs is through DNA methylation of the promoter region rather than histone deacetylation or mutation. IntroductionHead and neck squamous cell carcinoma (HNSCC) is one of the most frequently occurring malignancies and a major cause of morbidity and mortality (1,2). Oral cancer is the most common among the HNSCCs and the most frequently occurring oral cancer is squamous cell carcinoma (OSCC), which accounts for more than 90% of all oral malignancies (3). The number of OSCC cases that occur worldwide annually exceeds 300,000 (4). The mechanisms behind tumor progression of OSCC are known to a limited extent, indicating a clear need for comprehensive knowledge that can lead to more specific and effective molecular target.Microarray technology facilitates simultaneous evaluation of thousands of genes in a specimen. The results of microarray analysis provide researchers with high throughput screening to study the roles played by specific genes in cancer development and progression. We previously reported gene expression profiling of OSCC to identify cancer-related genes (5,6).The four and a half LIM domains (FHL) family of genes is characterized by LIM domains, a term derived from the first letters of three transcription factors: Lin-11, Isl-1 and Mec-3. Because the LIM domains provide protein-protein binding interfaces, the FHL genes play an important role in cellular events such as focal adhesion and differentiation by repressing or ac...

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“…The multifunctional A isoform of the RAS-association domain family 1 (RASSF1A) and adenomatous polyposis coli (APC) genes belong to the group of highly methylated genes found in many types of cancers, including BC, 10 and their methylation levels increase from the preinvasive and early stage of BC through tumorigenesis. 11,12 The tumor suppressor gene RASSF1A is functionally involved in apoptotic signaling, mitotic progression, and microtubule stabilization 10,13 ; therefore, its inactivation deregulates these events. The APC is an antagonist of the Wnt signaling pathway and is involved in the transcriptional activation, apoptosis, adhesion, and migration of cells.…”

Section: Translational Significancementioning

confidence: 99%

CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers

Fridrichová

Smolkova

Kajabova

et al. 2015

Translational Research

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Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype

Cited by 64 publications

References 43 publications

Methylation profiling identified novel differentially methylated markers includingOPCMLandFLRT2in prostate cancer

Methylation profiling identified novel differentially methylated markers includingOPCMLandFLRT2in prostate cancer

High prevalence of epigenetic inactivation of the human four and a half LIM domains 1 gene in human oral cancer

CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers

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