Meduloblastoma pediatrikoaren pronostikorako markatzaile molekularren identifikazioa

Abstract

Medulloblastoma is a very heterogeneous malignancy at both clinical and molecular levels. In recent years, thanks to the development of massive and whole genome sequencing techniques, many specific mutations have been discovered within each medulloblastoma subtype. Therefore, this study aimed to design a panel of somatic mutations and genes to allow the early recognition of poor prognosis patients or those that will develop resistance to therapy. With this aim, a systematic review was performed to identify all information available in the literature regarding mutations in genes involved in the development of pediatric medulloblastoma. We searched in PubMed database using the keywords and subject terms (Medulloblastoma*) AND (“mutation*” OR “genetic alteration*” OR “genetic variation*”). The original search provided 588 records, from which 62 were finally selected. Out of the 197 identified genes found in those records, 21 showed mutational frequencies higher than 2% and 5 (TP53, CTNNB1, PTCH1, SUFU and KDM6A) could be useful at diagnosis because of their prognostic value or because they were specific of a single subtype. The analysis of these genes could help achieve more individualized therapies based on molecular profile.; Meduloblastoma klinika eta oinarri molekular heterogeneoa duen minbizia da. Azken urteotan, genoma osoko eta sekuentziazio masiboko teknika molekularren garapenaren ondorioz, meduloblastoma pediatrikoan parte hartzen duten mutazio asko identifikatzea ahalbidetu da. Hortaz, lanaren helburua izan zen meduloblastoma pediatrikoaren pronostikoan edota terapian lagundu dezakeen gene eta mutazio somatikoen panel baten diseinua egitea. Horretarako, meduloblastoma pediatrikoan eragina duten geneei buruzko informazioa duen literaturaren berrikuspen sistematikoa egin zen. Bilaketarako Pubmed datubase bibliografikoa erabili zen, honako termino hauek erabiliz: (Medulloblastoma*) AND ("mutation*" OR "genetic alteration*" OR "genetic variation*"). Berrikuspen bibliografikoaren ondoren, hasieran zeuden 588 artikuluetatik 62 artikulutan 197 gene identifikatu ziren. Horietatik, % 2 baino gehiagoko mutazio-maiztasuna zuten 21 gene aurkitu ziren, eta diagnosiaren momentuan balio pronostikoa edo meduloblastoma azpimoten ezaugarri ziren 5 gene (TP53, CTNNB1, PTCH1, SUFU eta KDM6A). Gene horiek analizatuz gero, profil molekularrean oinarritutako tratamendu indibidualizatuak doitu litezke.