Identification of New Genetic Clusters in Glioblastoma Multiforme: <i>EGFR</i> Status and <i>ADD3 </i>Losses Influence Prognosis

• Main Authors: Lara Navarro, Teresa San-Miguel, Javier Megías, Nuria Santonja, Silvia Calabuig, Lisandra Muñoz-Hidalgo, Pedro Roldán, Miguel Cerdá-Nicolás, Concha López-Ginés
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Cells
• Subjects: glioblastoma; <i>IDH</i>; ADD3; EGFR; survival; high throughout techniques
• Online Access: https://www.mdpi.com/2073-4409/9/11/2429

Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. <i>EGFR</i> amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of <i>EGFR</i>vIII and FISH analysis for <i>EGFR</i> amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations between <i>EGFR</i> amplification and/or <i>EGFR</i>vIII, and SCNA in <i>CDKN2A, MSH6, MTAP</i> and <i>ADD3</i>. Interestingly, we found that both <i>EGFR</i>vIII and losses on <i>ADD3</i> were independent markers of bad prognosis (<i>p</i> = 0.028 and 0.014, respectively). Finally, we got an unsupervised hierarchical classification that differentiated three clusters of patients based on their genetic alterations. It offered a landscape of <i>EGFR</i> co-alterations that may improve the comprehension of the mechanisms underlying GB aggressiveness. Our findings can help in defining different genetic profiles, which is necessary to develop new and different approaches in the management of our patients.