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Bhak, Jong
The Genomics Institute of UNIST (TGI)
Research Interests
  • Geromics, genomics, bioinformatics, protein Engineering, OMICS

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

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dc.contributor.authorPhi, Ji Hoonko
dc.contributor.authorPark, Ae Kyungko
dc.contributor.authorLee, Seminko
dc.contributor.authorChoi, Seung Ahko
dc.contributor.authorBaek, In-Pyoko
dc.contributor.authorKim, Porako
dc.contributor.authorKim, Eun-Hyeko
dc.contributor.authorPark, Hee Chulko
dc.contributor.authorKim, Byung Chulko
dc.contributor.authorBhak, Jongko
dc.contributor.authorPark, Sung-Hyeko
dc.contributor.authorLee, Ji Yeounko
dc.contributor.authorWang, Kyu-Changko
dc.contributor.authorKim, Dong-Seokko
dc.contributor.authorShim, Kyu Wonko
dc.contributor.authorKim, Se Hoonko
dc.contributor.authorKim, Chae-Yongko
dc.contributor.authorKim, Seung-Kiko
dc.date.available2018-06-07T10:58:23Z-
dc.date.created2018-06-05ko
dc.date.issued201806ko
dc.identifier.citationACTA NEUROPATHOLOGICA, v.135, no.6, pp.939 - 953ko
dc.identifier.issn0001-6322ko
dc.identifier.urihttp://scholarworks.unist.ac.kr/handle/201301/24172-
dc.identifier.urihttps://link.springer.com/article/10.1007/s00401-018-1845-8ko
dc.description.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 in PDGFRA with augmented expression in the secondary glioblastomas after radiotherapy, implicating PDGFRA 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 of TP53 including 17p loss or germline/somatic mutations were also found in most of the secondary glioblastomas after radiotherapy, indicating a crucial role of TP53 alteration in the process. On the other hand, analysis of recurrent medulloblastomas revealed that the most prevalent alterations are the loss of 17p region including TP53 and gain of 7q region containing EZH2 which already exist in primary tumors. The 7q gain events are frequently accompanied by high expression levels of EZH2 in both primary and recurrent medulloblastomas, which provides a clue to a new therapeutic target to prevent recurrence. Considering the fact that it is often challenging to differentiate between recurrent medulloblastomas and secondary glioblastomas after radiotherapy, our findings have major clinical implications both for correct diagnosis and for potential therapeutic interventions in these devastating diseases.ko
dc.languageENGko
dc.publisherSPRINGERko
dc.subjectMedulloblastomako
dc.subjectRecurrenceko
dc.subjectSecondary glioblastoma after radiotherapyko
dc.subjectGenomic analysisko
dc.titleGenomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomasko
dc.typeARTICLEko
dc.identifier.pid2988null
dc.identifier.pid1842null
dc.identifier.rimsid30358ko
dc.identifier.scopusid2-s2.0-85047185354ko
dc.identifier.wosid000432296500009ko
dc.type.rimsAko
dc.identifier.doihttp://dx.doi.org/10.1007/s00401-018-1845-8ko
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