Comprehensive somatic mutational analysis in glioblastoma: Implications for precision medicine approaches

• Published in: PloS one 2024-01, Vol.19 (1), p.e0295698-e0295698
• Main Authors: Azimi, Parisa, Karimpour, Mina, Yazdanian, Taravat, Totonchi, Mehdi, Ahmadiani, Abolhassan
• Format: Article
• Language: English
• Subjects: Amino acid sequence; Amino acids; Amino Acids - genetics; Analysis; Biology and Life Sciences; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Classification; Datasets; Development and progression; Diagnosis; Evaluation; Gene amplification; Gene expression; Gene mutations; Genetic aspects; Genomes; Glial cells; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma multiforme; Glioma; Health aspects; Humans; Malignancy; Medical prognosis; Medical research; Medicine and Health Sciences; Medicine, Experimental; Mutation; Patients; Precision Medicine; Radiation therapy; Research and Analysis Methods; Sensitivity analysis; Survival; Survival analysis; Temozolomide; Temozolomide - therapeutic use; Therapeutic applications; Therapeutic targets; Tumors; Whole genome sequencing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0295698

Glioblastoma multiforme (GBM), a malignant neoplasm originating from glial cells, remains challenging to treat despite the current standard treatment approach that involves maximal safe surgical resection, radiotherapy, and adjuvant temozolomide chemotherapy. This underscores the critical need to identify new molecular targets for improved therapeutic interventions. The current study aimed to explore the somatic mutations and potential therapeutic targets in GBM using somatic mutational information from four distinct GBM datasets including CGGA, TCGA, CPTAC and MAYO-PDX. The analysis included the evaluation of whole exome sequencing (WES) of GBM datasets, tumor mutation burden assessment, survival analysis, drug sensitivity prediction, and examination of domain-specific amino acid changes. The results identified the top ten commonly altered genes in the aforementioned GBM datasets and patients with mutations in OBSCN and AHNAK2 alone or in combination had a more favorable overall survival (OS). Also, the study identified potential drug sensitivity patterns in GBM patients with mutations in OBSCN and AHNAK2, and evaluated the impact of amino acid changes in specific protein domains on the survival of GBM patients. These findings provide important insights into the genetic alterations and somatic interactions in GBM, which could have implications for the development of new therapeutic strategies for this aggressive malignancy.