Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma

ABSTRACTCutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates between stages. Importantly, a direct comparison of low-risk and high-risk stages revealed epigenetic traits characteristic of high-risk tumours. Finally, a prognostic prediction model in cSCC patients identified a methylation signature able to predict the overall survival of patients. Thus, the analysis of DNA-methylation in cSCC revealed changes during the evolution of the disease through the different stages that can be of great value not only in the diagnosis but also in the prognosis of the disease.

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Genome-wide DNA methylation profiling of esophageal squamous cell carcinoma from global high-incidence regions identifies crucial genes and potential cancer markers

Cancer Research ◽

10.1158/0008-5472.can-20-3445 ◽

2021 ◽

pp. canres.3445.2020

Author(s):

Fazlur Rahman Talukdar ◽

Sheila C Soares Lima ◽

Rita Khoueiry ◽

Ruhina Shirin Laskar ◽

Cyrille Cuenin ◽

...

Keyword(s):

Dna Methylation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Markers ◽

Genome Wide ◽

High Incidence ◽

Dna Methylation Profiling ◽

Potential Cancer ◽

Methylation Profiling

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Faculty Opinions recommendation of Surgical monotherapy versus surgery plus adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma: a systematic review of outcomes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718484006.793496924 ◽

2014 ◽

Author(s):

Desiree Ratner

Keyword(s):

Systematic Review ◽

Squamous Cell Carcinoma ◽

High Risk ◽

Cell Carcinoma ◽

Squamous Cell ◽

Adjuvant Radiotherapy ◽

Cutaneous Squamous Cell Carcinoma

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Faculty Opinions recommendation of Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725486356.793508151 ◽

2015 ◽

Author(s):

Ian Maher ◽

Stephanie R Jackson Cullison

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Prospective Study ◽

Sentinel Node ◽

Cell Carcinoma ◽

Head And Neck ◽

Sentinel Node Biopsy ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Node Biopsy

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Exploring Differentially Methylated Genes in Vulvar Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13143580 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3580

Author(s):

Shatavisha Dasgupta ◽

Patricia C. Ewing-Graham ◽

Sigrid M. A. Swagemakers ◽

Thierry P. P. van den Bosch ◽

Peggy N. Atmodimedjo ◽

...

Keyword(s):

Dna Methylation ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Dna Sequences ◽

Cpg Island ◽

Epigenetic Modification ◽

Vulvar Squamous Cell Carcinoma ◽

Differentially Methylated Genes ◽

Methylation Profiling

DNA methylation is the most widely studied mechanism of epigenetic modification, which can influence gene expression without alterations in DNA sequences. Aberrations in DNA methylation are known to play a role in carcinogenesis, and methylation profiling has enabled the identification of biomarkers of potential clinical interest for several cancers. For vulvar squamous cell carcinoma (VSCC), however, methylation profiling remains an under-studied area. We sought to identify differentially methylated genes (DMGs) in VSCC, by performing Infinium MethylationEPIC BeadChip (Illumina) array sequencing, on a set of primary VSCC (n = 18), and normal vulvar tissue from women with no history of vulvar (pre)malignancies (n = 6). Using a false-discovery rate of 0.05, beta-difference (Δβ) of ± 0.5, and CpG-island probes as cut-offs, 199 DMGs (195 hyper-methylated, 4 hypo-methylated) were identified for VSCC. Most of the hyper-methylated genes were found to be involved in transcription regulator activity, indicating that disruption of this process plays a vital role in VSCC development. The majority of VSCCs harbored amplifications of chromosomes 3, 8, and 9. We identified a set of DMGs in this exploratory, hypothesis-generating study, which we hope will facilitate epigenetic profiling of VSCCs. Prognostic relevance of these DMGs deserves further exploration in larger cohorts of VSCC and its precursor lesions.

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