Oliveira Ricardo Cunha de, Cavalcante Giovanna C, Soares-Souza Giordano B
Laboratório de Genética Humana e Médica, Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Pará, Belém 66075-110, Pará, Brazil.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, São Paulo, Brazil.
Int J Mol Sci. 2024 Nov 23;25(23):12585. doi: 10.3390/ijms252312585.
Energy metabolism is a fundamental aspect of the aggressiveness and invasiveness of breast cancer (BC), the neoplasm that most affects women worldwide. Nonetheless, the impact of genetic somatic mutations on glycolysis and oxidative phosphorylation (OXPHOS) genes in BC remains unclear. To fill these gaps, the mutational profiles of 205 screened genes related to glycolysis and OXPHOS in 968 individuals with BC from The Cancer Genome Atlas (TCGA) project were performed. We carried out analyses to characterize the mutational profile of BC, assess the clonality of tumors, identify somatic mutation co-occurrence, and predict the pathogenicity of these alterations. In total, 408 mutations in 132 genes related to the glycolysis and OXPHOS pathways were detected. The , , , , , , , and genes are also associated with the tumorigenesis process in other types of cancer, as are the genes , , and which had been previously described as oncogenes in BC, with whom the target genes of this work were associated. Seven mutations were identified and highlighted due to the high pathogenicity, which are present in more than one of our results and are documented in the literature as being correlated with other diseases. These mutations are rs267606829 (), COSV53860306 (), rs201634181 (), rs774052186 (), rs119103242 (), rs1436643226 (), and rs104894677 (). They could be further investigated as potential biomarkers for diagnosis, prognosis, and treatment of BC patients.
能量代谢是乳腺癌（BC）侵袭性和转移性的一个基本方面，乳腺癌是全球影响女性最多的肿瘤。尽管如此，基因体细胞突变对BC中糖酵解和氧化磷酸化（OXPHOS）基因的影响仍不清楚。为了填补这些空白，我们对来自癌症基因组图谱（TCGA）项目的968例BC患者中205个与糖酵解和OXPHOS相关的筛选基因进行了突变分析。我们进行了分析以表征BC的突变特征，评估肿瘤的克隆性，识别体细胞突变共现情况，并预测这些改变的致病性。总共检测到132个与糖酵解和OXPHOS途径相关基因中的408个突变。 、 、 、 、 、 、 和 基因也与其他类型癌症的肿瘤发生过程相关， 、 和 基因在BC中先前被描述为癌基因，本研究的靶基因与之相关。由于高致病性，我们鉴定并突出了7个突变，这些突变在我们的多个结果中出现，并且在文献中记载与其他疾病相关。这些突变是rs267606829（ ）、COSV53860306（ ）、rs201634181（ ）、rs774052186（ ）、rs119103242（ ）、rs1436643226（ ）和rs104894677（ ）。它们可作为BC患者诊断、预后和治疗的潜在生物标志物进行进一步研究。
