Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
oleh: Imran Khan, Esra Büşra Işık, Sadaf Mahfooz, Asif M. Khan, Mustafa Aziz Hatiboglu
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2023-03-01 |
Deskripsi
Background: Glioblastoma poses an inevitable threat to patients despite aggressive therapy regimes. It displays a great level of molecular heterogeneity and numerous substitutions in several genes have been documented. Next-generation sequencing techniques have identified various molecular signatures that have led to a better understanding of the molecular pathogenesis of glioblastoma. In this limited study, we sought to identify genetic variants in a small number of rare patients with aggressive glioblastoma. Methods: Five tumor tissue samples were isolated from four patients with rapidly growing glioblastoma. Genomic DNA was isolated and whole exome sequencing was used to study protein-coding regions. Generated FASTQ files were analyzed and variants were called for each sample. Variants were prioritized with different approaches and functional annotation was applied for the detrimental variants. Results: A total of 49,780 somatic variants were identified in the five glioblastoma samples studied, with the majority as missense substitutions. The top ten genes with the highest number of substitutions were <i>MUC3A</i>, <i>MUC4</i>, <i>MUC6</i>, <i>OR4C5</i>, <i>PDE4DIP</i>, <i>AHNAK2</i>, <i>OR4C3</i>, <i>ZNF806</i>, <i>TTN</i>, and <i>RP1L1</i>. Notably, variant prioritization after annotation indicated that the <i>MTCH2</i> (Chr11: 47647265 A>G) gene sequence change was putative deleterious in all of the aggressive tumor samples. Conclusion: The <i>MTCH2</i> (Chr11: 47647265 A>G) gene substitution was identified as putative deleterious in highly aggressive glioblastomas, which merits further investigation. Moreover, a high tumor mutation burden was observed, with a signature of the highest substitutions in <i>MUC3A</i>, <i>MUC4</i>, <i>MUC6</i>, <i>OR4C5</i>, <i>PDE4DIP</i>, <i>AHNAK2</i>, <i>OR4C3</i>, <i>ZNF806</i>, <i>TTN</i>, and <i>RP1L1</i> genes. The findings provide critical, initial data for the further rational design of genetic screening and diagnostic approaches against aggressive glioblastoma.