In Silico Analysis of Epidermal Growth Factor Receptor Gene Polymorphisms and Their Potential Relevance in Acute Myeloid Leukemia
Year: 2026
Type: article
Abstract: Background The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase involved in cellular proliferation, survival and differentiation. Although extensively studied in solid tumors, EGFR has also been detected at the protein level in a subset of acute myeloid leukemia (AML) samples, being functionally active in approximately 15% of patients. These findings raised interest in EGFR as a therapeutic target in AML, particularly regarding tyrosine kinase inhibitors such as erlotinib, although clinical results have been modest. Aim To identify EGFR polymorphisms registered in public databases, classify their potential functional impact using an integrated prediction platform, and discuss their possible relevance in acute myeloid leukemia. Materials and methods This computational study was based on in silico analysis. EGFR polymorphisms were identified through the dbSNP database (NCBI), and a minimum allele frequency filter (Minor Allele Frequency – MAF) between 0.1 and 1.0 was applied for variant selection. The selected variants were submitted to the PredictSNP2.0 platform, which integrates different functional prediction algorithms and classifies alterations as neutral or deleterious. Complementary data were obtained from ClinVar, Ensembl, OMIM, RegulomeDB and UCSC Genome Browser. Results The initial search in dbSNP identified 85,415 variants associated with the EGFR gene. After the global allele frequency filter, 943 variants were selected for further analysis, of which 306 unique variants were submitted to the PredictSNP2.0 platform. Preliminary results showed that 34 variants were classified as deleterious by more than 50% of the integrated prediction tools. Notably, the rs2072454 polymorphism, in the C/A and C/G substitutions, was considered deleterious by 100% of the algorithms evaluated. Discussion EGFR expression has been demonstrated in a subset of AML patients, with functional activation in approximately 15% of cases, indicating a possible role for this receptor in leukemic cell biology. Although erlotinib presented limited efficacy as a single agent in relapsed/refractory AML, preclinical evidence suggests off-target activity through pathways involved in AML differentiation. The consistent classification of common EGFR polymorphisms such as rs2072454 as deleterious suggests that structural alterations may compromise receptor function and influence the interaction with tyrosine kinase inhibitors, potentially affecting therapeutic response. Conclusion The in silico analysis identified EGFR polymorphisms with high deleteriousness scores, including rs2072454, which deserve further investigation. These variants may produce structural changes capable of impairing receptor function and modulating the response to tyrosine kinase inhibitors, representing candidates for functional validation in the context of acute myeloid leukemia.
Institution: Centro Universitário Nossa Senhora do Patrocínio
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223144794