Izlaganje sa skupa
https://doi.org/10.21857/ypn4oc4189
Abnormal orbits of genetic mechanisms in the formation of brain tumors
Nives Pećina-Šlaus
orcid.org/0000-0002-3334-7671
; Laboratory of Neurooncology, Croatian Institute for Brain Research, Šalata 12,10000 Zagreb, Croatia, Department of Biology, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
*
Anja Kafka
; Laboratory of Neurooncology, Croatian Institute for Brain Research, Šalata 12,10000 Zagreb, Croatia, Department of Biology, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
Petar Brlek
orcid.org/0000-0001-8022-4095
; Laboratory of Neurooncology, Croatian Institute for Brain Research, Šalata 12,10000 Zagreb, Croatia, St. Catherine Specialty Hospital, Branimirova 71E, 10000 Zagreb, Croatia.
Niko Njirić
; Laboratory of Neurooncology, Croatian Institute for Brain Research, Šalata 12,10000 Zagreb, Croatia, Department of Neurosurgery, University Hospital Center “Zagreb”, School of Medicine, University of Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia.
* Dopisni autor.
Sažetak
In spite of recent progress, molecular mechanisms responsible for brain tumor formation are still inadequately
explained. These are very complex mechanisms that include changes in genes and proteins
involved in numerous vital cellular processes - proliferation, apoptosis, DNA repair, mobility, angiogenesis,
immune surveillance, genomic instability and cellular metabolism. The famous hallmarks of
cancer proposed by Hanahan and Weinberg in 2000. have been constantly upgraded and now number
14 characteristics. Latest additions include unlocking phenotypic plasticity, nonmutational epigenetic
reprogramming, polymorphic microbiomes, and cellular senescence. However, signal transduction
pathways are fundamental in the development and progression of cancer. The imbalances in cellular
signaling networks are also causative of brain tumors. The recent failure of a number of targeted
therapies, particularly for glioblastoma, shows that CNS tumors do not just respond to a single
pathway-driven targeted therapy. On the contrary, targeting multiple pathways simultaneously could
be an alternative way to overcome tumorigenesis. Our group is studying brain tumor genetics with
particular focus on Wnt signaling. We believe that genetic and expression changes are associated to
phenotypic characteristics and behavior of tumor cells. The results of in silico analysis by cBioPortal for
Cancer Genomics (Figure 1) database following Array Comparative Genomic Hybridization (aCGH)
and Genomic Identification of Significant Targets in Cancer (GISTIC) identified significantly deleted
regions: 9p21.3; 17p13.2; 10q24.2; 14q21.3; 1p36.11 and 13q12.11, but also amplified ones: 3q28;
12q13.3 and 21q22.3 in higher malignancy grades of gliomas. We identified copy number aberration
(CNA), pathways and genes that are biologically and functionally significant by the use of DAVID, an
enrichment analysis tool designed to estimate the biological relevance of a given collection of genes,
and data repository KEGG (Kyoto Encyclopedia of Genes and Genomes). It should be emphasized
that other cellular mechanisms are also crucial for the formation of brain tumors, for example oncogenic
roles of long non-coding RNAs in signaling regulation. Novel research focuses on the tumor
microenvironment and glioma stem cells, the appearance of neoantigens and cellular senescence
that creates a specific SASP phenotype (senescence-associated secretory phenotype) responsible for
therapy resistance. All this contributes to a better understanding of the brain tumor genetic profile.
The highlighted molecular changes can offer prognostic markers and directions for the development of
improved treatment.
Ključne riječi
genetic profiles of brain tumors, cBioPortal, aCGH, GISTIC
Hrčak ID:
333469
URI
Datum izdavanja:
25.6.2025.
Posjeta: 322 *