DNA Methylation: An Epigenetic mechanism in oral squamous cell carcinoma

2014 ◽  
Vol 4 (2) ◽  
pp. 33-41
Author(s):  
Vikram Bhatia ◽  
Madhu Mati Goel ◽  
Madhu Mati Goel ◽  
Annu Makker ◽  
Annu Makker
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Precancerous Lesions ◽  
Genetic Alterations ◽  
Epigenetic Mechanism ◽  
Alternative Mechanism ◽  
Epigenetic Alterations

Oral squamous cell carcinoma (OSCC) is one of the most common malignan-cies worldwide, despite the fact that during the last decade numerous ad-vancements have been made in its detection, prevention and treatment. Screening and early detection are assumed to decrease the morbidity and mortality associated with OSCC. Accurate diagnosis of precancerous reactive or inflammatory lesions via conventional visual and tactile examination is still problematic. Although many efforts have been made to define the molecular signatures that identify the clinical outcome of OSCC, still there is lack of a reliable prognostic molecular marker. The transformation from normal epi-thelium to pre-malignancy, and finally to oral carcinoma is a multistep pro-cess accompanied by accumulation of genetic and epigenetic alterations. Unlike genetic alterations, epigenetic changes are heritable and potentially reversible. In recent years, epigenetic inactivation of genes by promoter DNA hypermethylation has been recognized as an important and alternative mechanism of OSCC initiation and progression. DNA methylation of promot-er region occurs not only in OSCC but it has also been found in precancerous lesions. The aim of the present review is to assess the current state of knowledge on the epigenetic alterations observed in the pathogenesis of OSCC; focusing mainly on DNA methylation changes.

scholarly journals DNA Methylation Markers from Negative Surgical Margins Can Predict Recurrence of Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2915
Author(s):  
Bruna Pereira Sorroche ◽  
Fazlur Rahman Talukdar ◽  
Sheila Coelho Soares Lima ◽  
Matias Eliseo Melendez ◽  
Ana Carolina de Carvalho ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Recurrence ◽  
Surgical Margins ◽  
Risk Scores ◽  
Marker Panel ◽  
Specificity And Sensitivity

The identification of molecular markers in negative surgical margins of oral squamous cell carcinoma (OSCC) might help in identifying residual molecular aberrations, and potentially improve the prediction of prognosis. We performed an Infinium MethylationEPIC BeadChip array on 32 negative surgical margins stratified based on the status of tumor recurrence in order to identify recurrence-specific aberrant DNA methylation (DNAme) markers. We identified 2512 recurrence-associated Differentially Methylated Positions (DMPs) and 392 Differentially Methylated Regions (DMRs) which were enriched in cell signaling and cancer-related pathways. A set of 14-CpG markers was able to discriminate recurrent and non-recurrent cases with high specificity and sensitivity rates (AUC 0.98, p = 3 × 10−6; CI: 0.95–1). A risk score based on the 14-CpG marker panel was applied, with cases classified within higher risk scores exhibiting poorer survival. The results were replicated using tumor-adjacent normal HNSCC samples from The Cancer Genome Atlas (TCGA). We identified residual DNAme aberrations in the negative surgical margins of OSCC patients, which could be informative for patient management by improving therapeutic intervention. This study proposes a novel DNAme-based 14-CpG marker panel as a promising predictor for tumor recurrence, which might contribute to improved decision-making for the personalized treatment of OSCC cases.

scholarly journals Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

2020 ◽  
Vol 9 (4) ◽  
pp. 1035 ◽  
Author(s):  
Yasmen Ghantous ◽  
Aysar Nashef ◽  
Imad Abu-Elnaaj
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Features ◽  
Squamous Cell ◽  
Methylation Status ◽  
Recurrence Free Survival ◽  
Epigenetic Alterations ◽  
Free Survival

Oral squamous cell carcinoma (OSCC) is a fatal disease caused by complex interactions between environmental, genomic, and epigenetic alterations. In the current study, we aimed to identify clusters of genes whose promoter methylation status correlated with various tested clinical features. Molecular datasets of genetic and methylation analysis based on whole-genome sequencing of 159 OSCC patients were obtained from the The Cancer Genome Atlas (TCGA) data portal. Genes were clustered based on their methylation status and were tested for their association with demographic, pathological, and clinical features of the patients. Overall, seven clusters of genes were revealed that showed a significant association with the overall survival/recurrence free survival of patients. The top ranked genes within cluster 4, which showed the worst prognosis, primarily acted as paraneoplastic genes, while the genes within cluster 6 primarily acted as anti-tumor genes. A significant difference was found regarding the mean age in the different clusters. No significant correlation was found between the tumor staging and the different clusters. In conclusion, our result provided a proof-of-principle for the existence of phenotypic diversity among the epigenetic clusters of OSCC and demonstrated the utility of the use epigenetics alterations in devolving new prognostic and therapeutics tools for OSCC patients.

Multi-Region Sequence Analysis of a Pregnancy-Related Oral Squamous Cell Carcinoma Exhibiting Low-Level Aggressive Behavior

2019 ◽  
Vol 28 (2) ◽  
pp. 188-195
Author(s):  
Davide Bartolomeo Gissi ◽  
Andrea Gabusi ◽  
Achille Tarsitano ◽  
Roberto Rossi ◽  
Tiziana Balbi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Aggressive Behavior ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Field Cancerization ◽  
Tumor Mass ◽  
Dna Mutation ◽  
Low Level

We analyzed the genetic and epigenetic profiles of an oral squamous cell carcinoma affecting a 41-year-old pregnant female. The patient presented with an oral mass located at the hard and soft palate with bone involvement and lymph node metastases (T4N1M0). She had been treated with multimodal radiotherapy and chemotherapy, and she is currently alive with no evidence of disease 8 years after treatment. DNA methylation and DNA mutation analyses were used to analyze multiple samples from the tumor mass and from the non-neoplastic mucosa to verify tumor heterogeneity. Genetic and epigenetic analyses revealed the presence of one shared TP53 driver mutation with the same DNA methylation profile in each of the 3 areas of the tumor mass; only 2 additional passenger mutations were detected, suggesting a simple clonal homogeneous carcinoma, which usually is associated with low-level aggressive behavior. Additionally, no genetic or epigenetic alteration in the non-neoplastic oral mucosa was detected, demonstrating the absence of field cancerization. The low aggressiveness of the lesion was confirmed by the patient being free of disease at a long-term follow-up examination. These data suggest a different molecular transformation pathway in pregnancy-related oral squamous cell carcinomas, providing new perspectives for further investigation.

scholarly journals Recurrent chromosomal and epigenetic alterations in oral squamous cell carcinoma and its putative premalignant condition oral lichen planus

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215055 ◽  
Author(s):  
Christopher G. Németh ◽  
Christoph Röcken ◽  
Reiner Siebert ◽  
Jörg Wiltfang ◽  
Ole Ammerpohl ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Lichen Planus ◽  
Squamous Cell ◽  
Oral Lichen Planus ◽  
Epigenetic Alterations ◽  
Premalignant Condition ◽  
Oral Lichen

DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma

2013 ◽  
Vol 18 (3) ◽  
pp. 801-808 ◽  
Author(s):  
Yung-Kai Huang ◽  
Bou-Yu Peng ◽  
Chia-Yo Wu ◽  
Chien-Tien Su ◽  
Hui-Chen Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell

scholarly journals SPINK7 expression changes accompanied by HER2, P53 and RB1 can be relevant in predicting oral squamous cell carcinoma at a molecular level

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gina Pennacchiotti ◽  
Fabio Valdés-Gutiérrez ◽  
Wilfredo Alejandro González-Arriagada ◽  
Héctor Federico Montes ◽  
Judith Maria Roxana Parra ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Precancerous Lesions ◽  
Morbidity Rate ◽  
Control Group ◽  
High Morbidity ◽  
Less Invasive ◽  
High Morbidity Rate

AbstractThe oral squamous cell carcinoma (OSCC), which has a high morbidity rate, affects patients worldwide. Changes in SPINK7 in precancerous lesions could promote oncogenesis. Our aim was to evaluate SPINK7 as a potential molecular biomarker which predicts OSCC stages, compared to: HER2, TP53, RB1, NFKB and CYP4B1. This study used oral biopsies from three patient groups: dysplasia (n = 33), less invasive (n = 28) and highly invasive OSCC (n = 18). The control group consisted of clinically suspicious cases later to be confirmed as normal mucosa (n = 20). Gene levels of SPINK7, P53, RB, NFKB and CYP4B1 were quantified by qPCR. SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also, SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal–Wallis test and Dunn's post-hoc with a p < 0.05 significance was used to analyze data. In OSCC, the SPINK7 expression had down regulated while P53, RB, NFKB and CYP4B1 had up regulated (p < 0.001). SPINK7 had also diminished in TCGA patients (p = 2.10e-6). In less invasive OSCC, SPINK7 and HER2 proteins had decreased while TP53 and RB1 had increased with respect to the other groups (p < 0.05). The changes of SPINK7 accompanied by HER2, P53 and RB1 can be used to classify the molecular stage of OSCC lesions allowing a diagnosis at molecular and histopathological levels.

Sign in / Sign up

Export Citation Format

Share Document