Copy-number alterations reshape the classification of diffuse intrinsic pontine gliomas. First exome sequencing results of the BIOMEDE trial.
作者： Nysom K , Entz-Werle N , Blomgren K , Grill J , Faure-Conter C
DOI: 10.1101/2021.04.29.21256183
关键词: DNA repair 、 Exome sequencing 、 Oncology 、 Everolimus 、 Dasatinib 、 Precision medicine 、 PI3K/AKT/mTOR pathway 、 Internal medicine 、 Erlotinib 、 Mutation 、 Medicine
摘要: Diffuse intrinsic pontine gliomas (DIPG) is an incurable neoplasm occurring mainly in children for which no progress was made the last decades. The randomized phase II BIOMEDE trial compared three drugs (everolimus, dasatinib, erlotinib) combined with irradiation. present report describes whole exome sequencing (WES) results first 100 patients randomized. Copy-number-Alteration (CNA) unsupervised clustering identified four groups different outcomes and biology. This classification improved prognostication to models based on known biomarkers (Histone H3 TP53 mutations). cluster presenting complex genomic rearrangements associated significantly worse outcome dysfunction. Mutation CNA signatures confirmed frequent alteration DNA repair machinery. With respect potential targetable pathways, PI3K/AKT/mTOR activation occurred all samples through multiples mechanisms. In conclusion, WES at diagnosis feasible most provides a better patient stratification theranostic information precision medicine.
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