Whole genome DNA methylation profiling of oral cancer in ethnic population of Meghalaya, North East India reveals novel genes

Khongsti, Shngainlang; Lamare, Frederick A.; Shunyu, Neizekhotuo Brian; Ghosh, Sahana; Maitra, Arindam; Ghosh, Srimoyee

doi:10.1016/j.ygeno.2017.09.002

Cited by 21 publications

(20 citation statements)

References 82 publications

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“…In the current study, DNA was extracted from pre-diagnostic peripheral blood, which may explain why comparatively more associations were observed for B-cell lymphoma compared with other types of cancer. Among these CpGs (Table 3), DNA methylation at cg25119261 ( HLA-DPB2 ) was reported to be differentially methylated between tumor and matched adjacent normal tissues in the context of oral squamous cell [36] and hepatocellular cancer [37]. These conclusions may corroborate our finding of overall cancer association at this site, although we used DNA methylation from pre-diagnostic blood.…”

Section: Discussionsupporting

confidence: 75%

Epigenetic drift association with cancer risk and survival, and modification by sex

Wong

Joo

et al. 2021

Preprint

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To investigate age- and sex-specific DNA methylation alterations related to cancer risk and survival, we used matched case-control studies of colorectal (N=835), gastric (N=170), kidney (N=143), lung (N=332), prostate (N=869) and urothelial (N=428) cancers, and mature B-cell lymphoma (N=438). Linear mixed-effects models were conducted to identify age-, sex- and age-by-sex-associated methylation markers using a discovery (controls) - replication (cases) strategy. Replication was further examined using summary statistics from Generation Scotland (GS). Associations between replicated markers and risk of and survival from cancer were assessed using conditional logistic regression and Cox models (hazard ratios [HR]), respectively. We found 32,659, 23,141 and 48 CpGs with replicated associations for age, sex and age-by-sex, respectively. The replication rates (GS summary data) for these CpGs were 94%, 86% and 91%, respectively. Significant signals for cancer risk and survival were identified at some individual age-related CpGs. There was a strong negative trend in the association between epigenetic drift and risk of colorectal cancer. Two CpGs overlapping TMEM49 and ARX genes were associated with survival of overall (HR=0.91, P=7.7×10−4) and colorectal (HR=1.52, P=1.8×10−4) cancer, respectively, with significant age-by-sex interaction. Our results may provide markers for cancer early detection and prognosis prediction.Simple SummaryAgeing is the strongest cancer risk factor, and men and women exhibit disparate risk profiles in terms of incidence and survival. DNA methylation is known to strongly vary by age and sex. Epigenetic drift refers to age-related DNA methylation changes and the tendency for increasing discordance between epigenomes over time, but it remains unknown to what extent the epigenetic drift might contribute to cancer risk and survival. The aims of this study were to identify age-associated, sex-associated and sexually dimorphic age-associated (age-by-sex-associated) DNA methylation markers and investigate whether age- and age-by-sex-associated markers are associated with cancer risk and survival. Our study, which used a total of 3,215 matched case-control pairs with DNA methylation in pre-diagnostic blood, is the first large study to examine the association between sex-specific epigenetic drift and cancer development and progression. The results may be useful for cancer early diagnosis and prediction of prognosis.

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Section: Discussionsupporting

confidence: 75%

Epigenetic drift association with cancer risk and survival, and modification by sex

Wong

Joo

et al. 2021

Preprint

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“…β value is calculated as the ratio of fluorescent signals from the methylated probes to the sum of the signals from the methylated and unmethylated probes as β = [M/(M + U + 100)], where M = methylated probe and U = unmethylated probe. The β value ranged from 0 to 1, while unmethylated probes had a β-value close to 0 and fully methylated probes had a β-value close to 1 ( Bibikova et al, 2011 ; Khongsti et al, 2017 ; The Cancer Genome Atlas Network, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…P16 , MGMT , DAPK , RASSF1 , MINT31 , EDNRB , KIF1A , DCC , P15 , hMLH 1 and E-cadherin genes in conjunction with HPV infection and tobacco usage have been correlated to oral cancer and other head and neck cancers among the Indian population ( Merlo et al, 1995 ; Viswanathan et al, 2003 ; Kaur et al, 2010 ; Choudhury and Ghosh, 2015 ). A recent study on the whole genome methylation profile for oral cancer was undertaken on a subset of the northeast India population ( Khongsti et al, 2017 ). However, no whole genome, candidate gene methylation or gene expression studies have been conducted on oropharyngeal cancer in India.…”

Section: Introductionmentioning

confidence: 99%

Whole Genome DNA Methylation and Gene Expression Profiling of Oropharyngeal Cancer Patients in North-Eastern India: Identification of Epigenetically Altered Gene Expression Reveals Potential Biomarkers

et al. 2020

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Oropharyngeal cancer is a subtype of head and neck squamous cell carcinoma that is associated with unique risk exposures like consumption of smokeless tobacco and areca nut and is highly prevalent in the northeastern region of India, especially Meghalaya. However, the underlying epigenetic and transcriptomic changes in this cancer type is yet to be delineated. We have undertaken a study on genome wide somatic alterations in the DNA methylation and transcriptome in oropharyngeal cancer patients from this region using genome wide techniques in paired tumors and adjacent normal tissues. By using integrative approaches, we have identified 194 epigenetically silenced and 241 epigenetically overexpressed genes in the tumor tissue of these patients. Pathways that are significantly enriched by these genes include the pathways of immune systems, such as the interleukin signaling pathways and Toll-like receptor signaling pathway. Also, osteoclast differentiation pathway was found to be epigenetically upregulated. The pathways enriched by the epigenetically downregulated genes were found to be predominantly those involved in xenobiotic metabolism and keratinization. Two major transcription factors – SPI1 and RUNX1 were identified as epigenetically dysregulated, which further modulates 129 downstream genes. Comparison of our observations with the head and neck cancer data from TCGA revealed distinct DNA methylation and gene expression landscapes which might be specific for oropharyngeal cancer. HPV DNA sequences were not detected in any of the tumor samples in RNA-Seq data. The results obtained in this study might provide improved understanding of the disease.

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“…However, hypomethylation events were also found to be distributed in shelves, in addition to CGIs and shores. In addition, more new DMRs specific to OSCC were identified, including five hypermethylated (GPR81, THSD7A, ADPRH, VSX1, and SLC35F1) and three hypomethylated regions (KRT6A, TM4SF19, and TMEM132B), indicating that these genes are worthy of further study as potential biomarkers for OSCC [ 75 , 76 ]. The source of samples for methylation testing would not be restricted to tissues, and saliva is also an excellent choice, given the noninvasive nature of its collection procedure.…”

Section: Panning For Goldmentioning

confidence: 99%

Biomarkers: paving stones on the road towards the personalized precision medicine for oral squamous cell carcinoma

et al. 2018

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Traditional therapeutics have encountered a bottleneck caused by diagnosis delay and subjective and unreliable assessment. Biomarkers can overcome this bottleneck and guide us toward personalized precision medicine for oral squamous cell carcinoma. To achieve this, it is important to efficiently and accurately screen out specific biomarkers from among the huge number of molecules. Progress in omics-based high-throughput technology has laid a solid foundation for biomarker discovery. With credible and systemic biomarker models, more precise and personalized diagnosis and assessment would be achieved and patients would be more likely to be cured and have a higher quality of life. However, this is not straightforward owing to the complexity of molecules involved in tumorigenesis. In this context, there is a need to focus on tumor heterogeneity and homogeneity, which are discussed in detail. In this review, we aim to provide an understanding of biomarker discovery and application for precision medicine of oral squamous cell carcinoma, and have a strong belief that biomarker will pave the road toward future precision medicine.

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Whole genome DNA methylation profiling of oral cancer in ethnic population of Meghalaya, North East India reveals novel genes

Cited by 21 publications

References 82 publications

Epigenetic drift association with cancer risk and survival, and modification by sex

Epigenetic drift association with cancer risk and survival, and modification by sex

Whole Genome DNA Methylation and Gene Expression Profiling of Oropharyngeal Cancer Patients in North-Eastern India: Identification of Epigenetically Altered Gene Expression Reveals Potential Biomarkers

Biomarkers: paving stones on the road towards the personalized precision medicine for oral squamous cell carcinoma

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