Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas

AbstractDespite great advances in understanding of molecular pathogenesis and achievement of a high cure rate in medulloblastoma, recurrent medulloblastomas are still dismal. Additionally, misidentification of secondary malignancies due to histological ambiguity leads to misdiagnosis and eventually to inappropriate treatment. Nevertheless, the genomic characteristics of recurrent medulloblastomas are poorly understood, largely due to a lack of matched primary and recurrent tumor tissues. We performed a genomic analysis of recurrent tumors from 17 pediatric medulloblastoma patients. Whole transcriptome sequencing revealed that a subset of recurrent tumors initially diagnosed as locally recurrent medulloblastomas are secondary glioblastomas after radiotherapy, showing high similarity to the non-G-CIMP proneural subtype of glioblastoma. Further analysis, including whole exome sequencing, revealed missense mutations or complex gene fusion events inPDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicatingPDGFRA as a putative driver in the development of secondary glioblastomas after treatment exposure. This result provides insight into the possible application of PDGFRA-targeted therapy in these second malignancies. Furthermore, genomic alterations ofTP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role ofTP53 alteration in the process. On the ...

Source: Acta Neuropathologica - April 11, 2018 Category: Neurology Source Type: research