Evolutionary study of oncogenes and tumor suppressor genes in breast carcinoma.

OBJECTIVES

Cancer involves abnormal cell proliferation and migration throughout the body. Genetic changes occurring in hereditary breast cancer led to the activation of oncogenes, resulting in gain-of-function effects. This study was designed to conduct a phylogenetic analysis of breast cancer-related oncogenes and tumor suppressor genes families in humans relevant to different species and their potential against breast cancer.

METHODS

The protein sequence data were retrieved from Ensembl Genome Browser and NCBI databases. BLAST searches were performed to obtain FASTA sequences of selected vertebrates. Multiple sequence alignment was conducted using ClustalW in MEGA X, followed by the construction of neighbor-joining phylogenetic trees in circular format. Tree robustness was assessed through bootstrap analysis with 500 pseudoreplicates.

RESULTS

Among the eleven oncogenes, the CBLC and JUN gene has two paralogues, BCL3, DDX6, FEV, MYB, KARAS, LCK, NUP214 and MPL had 5, while TFG have no paralogues. These gene families determine functional networks including transcriptional regulation, signaling cascades, receptors activity, and RNA processing, all influence breast cancer pathogenesis. In the 10 tumor suppressor genes, the CDH1, JAK2, PML, PTEN, GPC3, SOCS1, gene had 5 paralogues, EXT1 and WRN gene has 4, NPM1 has 2, VHL has 1 paralogue. These paralogues show corresponding molecular functions vital for tumor suppression and cellular homeostasis. The phylogenetic analysis exposed all studied genes share common evolutionary source in vertebrate lineage.

CONCLUSIONS

In conclusion, variability in paralogue numbers among oncogenes and tumor suppressor genes, with some genes having multiple paralogues and others, like TFG and VHL, having few or none was found. Phylogenetic trees highlighted evolutionary relationships among vertebrates.