RESUMEN
PURPOSE: Circumscribed gliomas -pilocytic astrocytomas (PA), gangliogliomas (GG), ependymomas (EP)- are mostly low-grade tumours but may progress to anaplasia and sometimes surgery can be challenging due to deep anatomical localization. Because of the high frequency of MAPK-pathway alterations and availability of targeted therapies for FGFR1 and BRAF-mutated tumors, we investigated these mutational hotspots in a cohort of adult circumscribed gliomas. METHODS: Adult patients (>15 years) with diagnosis of PA, GG, EP and DNET were retrospectively identified from two institutions databases. Genomic DNA was extracted from formalin-fixed paraffin-embedded or frozen samples and exons including codons 546 and 656 of FGFR1 and V600 of BRAF were sequenced. RESULTS: FGFR1 mutations were identified in 15/108 PA and were particularly frequent in optic pathway (6/9 vs. 9/108; p = 10-4). FGFR1 was mutated in 3/75 grade II versus 2/7 grade III GG (p = 0.05), 1/7 DNET, 1/100 EP grade II. We found 3/108 PA with BRAF pVal600Glu and 6/108 with p.Thr599_Val600insThr. The p.Val600Glu was found in 14/75 grade II GG. No EP were BRAF mutated. CONCLUSIONS: We report actionable targets, including frequent FGFR1 mutation in optic-pathway PA that makes them excellent candidates to anti-FGFR therapies, and BRAF non-canonical mutations in PA.
Asunto(s)
Neoplasias Encefálicas/genética , Glioma/genética , Proteínas Proto-Oncogénicas B-raf/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Astrocitoma/genética , Ependimoma/genética , Femenino , Ganglioglioma/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias Neuroepiteliales/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
Aneurysm is a multifactorial degenerative disease characterized by focal dilatation of blood vessels. Although abdominal aortic (AAA) and popliteal aneurysms (PAA) are the most common dilatative vascular diseases and share some features, a comparison between the different anatomical sites and the relative pathophysiological differences has not been established. In order to gain deeper insights to AAA and PAA, we have characterized the role of matrix remodelling, vascular cells phenotype depletion and the inflammatory process in both diseases. Results show a more extensive presence of T-cell, B-cell and monocyte-macrophage infiltration in AAA with respect to PAA. Concurring with this aspect, IL-6, IL-8 and MCP-1 are 10-fold increased in AAA. Moreover, MMP-9, and metalloproteinase inhibitor 3 (TIMP3) resulted up-regulated in AAA tissues. Regarding the catalytic activity, which is tightly related to the oxidative stress, we found an up-regulation of superoxide dismutase [Mn] mitochondrial (SODM), glutathione peroxidase 3 (GPX3) and peroxiredoxin-1 (PRDX1). Histological analyses clearly showed a massive elastin fragmentation in AAA. This may enhance the inflammatory response, which has a prevalent role in AAA, while PAA is mainly guided by a loss of the contractile phenotype. These findings suggest insight in these potentially devastating diseases in term of their progression, aiming to identify potential specific markers respectively for AAA and PAA treatment.