Nejvíce citovaný článek - PubMed ID 10329596
In this study, we provide a comprehensive clinical and molecular biological characterization of radiation-induced gliomas (RIG), including a risk assessment for developing gliomas. A cohort of 12 patients who developed RIG 9.5 years (3-31 years) after previous cranial radiotherapy for brain tumors or T-cell acute lymphoblastic leukemia was established. The derived risk of RIG development based on our consecutive cohort of 371 irradiated patients was 1.6% at 10 years and 3.02% at 15 years. Patients with RIG glioma had a dismal prognosis with a median survival of 7.3 months. We described radiology features that might indicate the suspicion of RIG rather than the primary tumor recurrence. Typical molecular features identified by molecular biology examination included the absence of Histon3 mutation, methylation profile of pedHGG-RTK1 and the presence of recurrent PDGFRA amplification and CDKN2A/B deletion. Of the two long-term surviving patients, one had gliomatosis cerebri, and the other had pleomorphic xanthoastrocytoma with BRAF V600E mutation. In summary, our experience highlights the need for tissue diagnostics to allow detailed molecular biological characterization of the tumor, differentiation of the secondary tumor from the recurrence of the primary disease and potentially finding a therapeutic target.
- MeSH
- astrocytom * patologie MeSH
- gliom * genetika radioterapie MeSH
- lidé MeSH
- mutace MeSH
- nádory mozku * genetika radioterapie MeSH
- protoonkogenní proteiny B-Raf genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- protoonkogenní proteiny B-Raf MeSH
Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.
- MeSH
- amplifikace genu * MeSH
- chromozomální delece MeSH
- dítě MeSH
- dospělí MeSH
- genetická transkripce MeSH
- genom lidský MeSH
- genová přestavba genetika MeSH
- gliom genetika patologie MeSH
- inhibitor p15 cyklin-dependentní kinasy metabolismus MeSH
- inhibitor p16 cyklin-dependentní kinasy metabolismus MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru patologie MeSH
- metylace DNA genetika MeSH
- mladiství MeSH
- mladý dospělý MeSH
- regulace genové exprese u nádorů MeSH
- růstový faktor odvozený z trombocytů - receptor alfa genetika metabolismus MeSH
- shluková analýza MeSH
- záření MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CDKN2A protein, human MeSH Prohlížeč
- CDKN2B protein, human MeSH Prohlížeč
- inhibitor p15 cyklin-dependentní kinasy MeSH
- inhibitor p16 cyklin-dependentní kinasy MeSH
- růstový faktor odvozený z trombocytů - receptor alfa MeSH