Methylation profiling of rectal cancer identifies novel markers of early-stage disease

Leong, Kai; Wei, Wenbin; Tannahill, Lesley; Caldwell, Germaine; Jones, Carolyn; Morton, Dion; Matthews, Glenn; Bach, Simon

doi:10.1002/bjs.7422

Cited by 44 publications

(29 citation statements)

References 36 publications

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“…Our study revealed that methylation frequency of APC is markedly increased in primary tumors, which was consistent with previous reports in rectal (Leong et al, 2011), breast (Mulligan et al, 2014), colorectal, and gastrointestinal cancers (Esteller et al, 2001). Furthermore, APC displayed higher degrees of methylation in patients with lymph node metastasis or higher TNM stages, which was also in accordance with results from breast cancer studies (Mulligan et al, 2014).…”

Section: Discussionsupporting

confidence: 93%

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

et al. 2016

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ABSTRACT. Head and neck squamous cell carcinoma (HNSCC) has become one of the most common forms of cancer worldwide. Hypermethylation-induced silencing of tumor-associated gene has been proposed as an important cofactor in cancer pathology. This paper aimed to characterize the gene methylation patterns in human papillomavirus (HPV) associated-HNSCC. TIMP3 and APC methylation status in neoplastic (N = 92) and non-neoplastic tissues (N = 92) of HNSCC as well as their association with HPV infection were investigated via methylation-specific PCR assays. Results indicated that methylation level of TIMP3 was markedly higher in HPV-positive tumors as compared with HPV-negative tumors. Both TIMP3 and APC methylation were associated with lymph node metastasis and higher clinical stage of tumors. Patients with methylation at TIMP3 or APC had worse prognoses as compared to those without these alterations. This is the first study that shows a possible linkage between HPV infection and APC methylation. Methylation patterns of tumor-related genes may contribute to different disease prognosis in HNSCC according to the HPV infection status.

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Section: Discussionsupporting

confidence: 93%

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

et al. 2016

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“…The absence of bisulfite conversion step is an other advantage of this method. Different studies reported a high correlation in results between standard method as bisulfite sequencing, pyrosequencing, methylation-specific PCR (MS-PCR) and MS-MLPA [ESR1, CDH13 (Paulsson et al, 2009), MGMT (Jeuken et al, 2007), RASSF1 (Buyru et al, 2009), CHFR, and RARB (Chen et al, 2007), APC and RARB (Leong et al, 2011)]. In this study, we compared GSTP1 MS-MLPA and bisulfite sequencing methylation results and found a perfect agreement between these techniques, confirming the reliability of the MS-MLPA assay.…”

Section: Discussionsupporting

confidence: 86%

GSTP1 hypermethylation is associated with reduced protein expression, aggressive disease and prognosis in neuroblastoma

Gumy‐Pause

Pardo

Khoshbeen-Boudal

et al. 2011

Genes Chromosomes & Cancer

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Epigenetic modifications such as methylation of CpG islands in tumor-suppressor gene promoter regions have been associated with tumor development in many human cancers. Using methylation specific multiplex ligation-dependent probe amplification method, we analyzed the methylation status of 35 different genes in 16 neuroblastoma (NB) cell lines and 50 NB tumor samples (NBs), and investigated whether specific hypermethylation was associated with biological and/or clinical parameters. Among the genes found hypermethylated, the effect of GSTP1 hypermethylation on mRNA and protein expression was also explored. The median number of hypermethylated genes was higher in cell lines compared to NBs (5.5 vs. 2). For eight genes, aberrant methylation of CpG-islands in NB was not (ESR1, PAX5, WT1, CADM1, MSH6, and CDKN2B) or very rarely (CDH13 and GSTP1) reported in literature. GSTP1 was found hypermethylated in 44% of the NB cell lines and in 33% of the stage 4-11qLOH -non MYCN-amplified high risk NBs. Hypermethylation was correlated with reduced mRNA and protein expression. In the whole NBs cohort, GSTP1 hypermethylation was less frequently detected (8%), but found to be associated with lower event-free (EFS) and overall survival. Hypermethylation of GSTP1 showed also association with lower EFS in high risk subgroups as stage 4 and older patients (≥547 days). Our results suggest that, as in several adult cancers, aberrant methylation of GSTP1 may contribute to the carcinogenetic process in NB and could be potentially used as a new marker leading to define an ultra-high risk subgroup.

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“…A methylation percentage for each probe was obtained using the following calculation, as described previously [22]: Methylation % ð Þ ¼ peak height of a given probe=mean height of control probes ð Þ with Hha1 peak height of a given probe=mean height of control probes ð Þ without Hha1 Â 100…”

Section: Dna Extractionmentioning

confidence: 99%

Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; potential marker of disease recurrence

Rengucci

Maio

Gardini

et al. 2014

J Exp Clin Cancer Res

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Background: Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods: A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry.

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Methylation profiling of rectal cancer identifies novel markers of early-stage disease

Abstract: Locus-specific hypermethylation was more prevalent in early- than late-stage disease. Hypermethylation of two or more of a panel of five tumour suppressor genes was associated with localized disease.

Cited by 44 publications

References 36 publications

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

Characterization of gene methylation in human papillomavirus associated-head and neck squamous cell carcinoma

GSTP1 hypermethylation is associated with reduced protein expression, aggressive disease and prognosis in neuroblastoma

Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; potential marker of disease recurrence

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