We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
EGFR Pathway-Based Gene Signatures of Druggable Gene Mutations in Melanoma, Breast, Lung, and Thyroid Cancers.
- Authors
Raevskiy, Mikhail; Sorokin, Maxim; Vladimirova, Uliana; Suntsova, Maria; Efimov, Victor; Garazha, Andrew; Drobyshev, Alexei; Moisseev, Aleksey; Rumiantsev, Pavel; Li, Xinmin; Buzdin, Anton
- Abstract
EGFR, BRAF, PIK3CA, and KRAS genes play major roles in EGFR pathway, and accommodate activating mutations that predict response to many targeted therapeutics. However, connections between these mutations and EGFR pathway expression patterns remain unexplored. Here, we investigated transcriptomic associations with these activating mutations in three ways. First, we compared expressions of these genes in the mutant and wild type tumors, respectively, using RNA sequencing profiles from The Cancer Genome Atlas project database (n = 3660). Second, mutations were associated with the activation level of EGFR pathway. Third, they were associated with the gene signatures of differentially expressed genes from these pathways between the mutant and wild type tumors. We found that the upregulated EGFR pathway was linked with mutations in the BRAF (thyroid cancer, melanoma) and PIK3CA (breast cancer) genes. Gene signatures were associated with BRAF (thyroid cancer, melanoma), EGFR (squamous cell lung cancer), KRAS (colorectal cancer), and PIK3CA (breast cancer) mutations. However, only for the BRAF gene signature in the thyroid cancer we observed strong biomarker diagnostic capacity with AUC > 0.7 (0.809). Next, we validated this signature on the independent literature-based dataset (n = 127, fresh-frozen tissue samples, AUC 0.912), and on the experimental dataset (n = 42, formalin fixed, paraffin embedded tissue samples, AUC 0.822). Our results suggest that the RNA sequencing profiles can be used for robust identification of the replacement of Valine at position 600 with Glutamic acid in the BRAF gene in the papillary subtype of thyroid cancer, and evidence that the specific gene expression levels could provide information about the driver carcinogenic mutations.
- Subjects
EPIDERMAL growth factor receptors; GENETIC mutation; THYROID cancer; BRAF genes; BREAST; RAS oncogenes; THYROID gland
- Publication
Biochemistry (00062979), 2021, Vol 86, Issue 11, p1477
- ISSN
0006-2979
- Publication type
Article
- DOI
10.1134/S0006297921110110