Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis

Bates, Timothy; Kennedy, Matthew; Diajil, Ameena Ryhan; Goodson, M.L.; Thomson, Peter; Doran, Emma; Farrimond, Heather; Thavaraj, Selvam; Sloan, Philip; Kist, Ralf; Robinson, Max

doi:10.1158/1055-9965.epi-15-0949

Cited by 13 publications

(10 citation statements)

References 46 publications

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“…In OSCC it ranges from 9% to 56% of cases, being more frequent in T3 and T4 stages. 46 However, other authors have concluded that there is no association between EGFR expression and EGFR CNG in OSCC. Moreover, neither of these changes was associated with clinicopathological features of OSCC.…”

Section: Detection Methods Of Egfr In Oral Cancermentioning

confidence: 98%

Dysregulation and detection methods of EGFR in oral cancer. A narrative review.

Somarriva

Fernández²,

Candia

et al. 2016

J Oral Res

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Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with an intracellular domain and tyrosine kinase function (TK) involved in cell proliferation. Dysfunctions in EGFR signaling pathways have been associated with oral malignant tumors such as oral squamous cell carcinoma (OSCC). Dysfunctions of EGFR may result from: increased EGF ligand; EGFR overexpression and copy number gain of the EGFR gene (EGFR CNG); EGFR mutations; failure in the downregulation of EGFR; and EGFR crosstalk. Of these alterations, overexpression of EGFR is by far the most studied dysfunction in OSCC. Clinicians should identify possible alterations of EGFR in the oral mucosa of patients, as EGFR can act as a biomarker for the diagnosis and prognosis of OSCC. Currently, there are several methods and techniques for detecting EGFR. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), are used to identify overexpression of EGFR, EGFR CNG and EGFR mutations, respectively. Detection of EGFR as a biomarker is key to identify any oral malignant transformation. Consequently, it becomes imperative to implement a non-invasive and inexpensive method of early diagnosis for OSCC in clinical practice.

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Section: Detection Methods Of Egfr In Oral Cancermentioning

confidence: 98%

Dysregulation and detection methods of EGFR in oral cancer. A narrative review.

Somarriva

Fernández²,

Candia

et al. 2016

J Oral Res

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“…OPMD cases for this study were selected from a previously studied cohort of OPMD patients 12 . A case was classified as having undergone MT when there was progression from an OPMD to oral squamous cell carcinoma (OSCC) after a period of six months or more from the time of the initial diagnosis of OPMD.…”

Section: Methodsmentioning

confidence: 99%

“…OPMD cases for this study were selected from a previously studied cohort of OPMD patients. 12 All histopathological assessments were performed following a modified three-tier system adapted from the work published by Speight et. al.…”

Section: Patientsmentioning

confidence: 99%

Gene expression changes associated with malignant transformation of oral potentially malignant disorders

Sathasivam

Casement

Bates

et al. 2020

J Oral Pathology Medicine

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Background A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed “non‐transforming” (NT) cases. Methods Total RNA was extracted from formalin‐fixed paraffin‐embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected P‐value was < 0.05. Results RNA yield was variable but RNA purity was good (A260/A280 > 1.90). Analysis of RNA‐Sequencing outputs revealed 41 genes (34 protein‐coding; 7 non‐coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from −2.63 to 2.48, with 23 protein‐coding genes being downregulated and 11 protein‐coding genes being upregulated in MT cases compared to NT cases. Conclusion Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the etiopathogenesis of OPMD and development of novel biomarkers.

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“…5 Various clinical, histopathological, and genomic factors have been suggested to be associated with an increased risk of malignant transformation of OLs. [12][13][14][15][16][17][18][19][20][21][22][23][24] However, there are currently no reliable biomarkers that can identify OLs with a high risk of developing into cancer. 17 Copy number alterations (CNAs), that is, amplifications/gains and losses of genes or chromosomal segments, are common alterations in head and neck squamous cell carcinomas (HNSCC) and include, for example, losses at 3p and 9p, and gains at 3q, 5p, 7p, and 8q.…”

Section: Introductionmentioning

confidence: 99%

Recurrent copy number alterations involving EGFR, CDKN2A, and CCND1 in oral premalignant lesions

Jäwert

Fehr

Öhman

et al. 2022

J Oral Pathology Medicine

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Background A major challenge in the management of patients with oral leukoplakia is the difficulty to identify patients at high risk of developing oral squamous cell carcinoma. Our knowledge about genomic alterations in oral leukoplakia, and in particular those that progress to oral squamous cell carcinoma, is scarce and there are no useful biomarkers that can predict the risk of malignant transformation. Methods Using a novel, custom‐made tissue microarray including 28 high‐risk oral leukoplakias and the corresponding oral squamous cell carcinomas from 14 cases that progressed to cancer, we assayed copy number alterations involving the oral squamous cell carcinoma driver genes CDKN2A, CCND1, EGFR, and MYC by fluorescence in situ hybridization. The copy number alterationss were correlated with clinicopathological data from all patients. Results Copy number alterations were identified in 14/24 oral leukoplakias, analyzable for one or more of the oral squamous cell carcinoma driver genes. EGFR was the most frequently altered gene in oral leukoplakias with amplification/gain in 43.5% followed by loss of CDKN2A (26.1%), gains of CCND1 (26.1%), and MYC (8.3%). Losses of CDKN2A were more common in oral leukoplakias progressing to oral squamous cell carcinoma compared to those that did not. Copy number alterations were more common in oral squamous cell carcinomas than in oral leukoplakias. Conclusions Our findings demonstrate that copy number alterations involving the oral squamous cell carcinoma drivers CDKN2A, EGFR, and CCND1 occur in oral leukoplakias and suggest a possible role for these genes in the development and/or progression of subsets of oral leukoplakias.

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Changes in Epidermal Growth Factor Receptor Gene Copy Number during Oral Carcinogenesis

Cited by 13 publications

References 46 publications

Dysregulation and detection methods of EGFR in oral cancer. A narrative review.

Dysregulation and detection methods of EGFR in oral cancer. A narrative review.

Gene expression changes associated with malignant transformation of oral potentially malignant disorders

Recurrent copy number alterations involving EGFR, CDKN2A, and CCND1 in oral premalignant lesions

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