RT info:eu-repo/semantics/article
T1 Somatic copy number alterations are associated with EGFR amplification  and shortened survival in patients with primary glioblastoma
A1 Muñoz-Hidalgo, Lisandra
A1 San-Miguel, Teresa
A1 Megías Vericat, Javier
A1 Monleón, Daniel
A1 Navarro Cerveró, Lara
A1 Roldán, Pedro
A1 Cerdá-Nicolás, Miguel
A1 López-Ginés, Concha
K1 Brain-Diseases
K1 Brain-cancer
K1 Oncology
K1 Brain
K1 Cancer
AB Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, theprognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration.In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of thepatients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes.Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumorsshowed histological features of aggressiveness. Interestingly, accumulation of CNAs, as a measure of tumor mutational burden, was frequent and significantly associated to shortened survival. EGFR-amplified GBMs displayed both a higher number of concrete CNAs and ahigher global tumor mutational burden than their no EGFR-amplified counterparts. In addition to genetic changes previously described inGBM, we found PARK2 and LARGE1 CNAs associated to EGFR amplification. The set of genes analyzed allowed us to explore relevantsignaling pathways on GBM. Both PARK2 and LARGE1 are related to receptor tyrosine kinase/PI3K/PTEN/AKT/mTOR-signaling pathway. Finally, we found an association between the molecular pathways altered, EGFR amplification and a poor outcome.Our results underline the potential interest of categorizing GBM according to their EGFR amplification level and the usefulness of assessing the tumor mutational burden. These approaches would open new knowledge possibilities related to GBM biology and therapy.
SN 1522-8002
YR 2020
FD 2020
LK http://riull.ull.es/xmlui/handle/915/36160
UL http://riull.ull.es/xmlui/handle/915/36160
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 11-jun-2024