DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, June Koo | ko |
dc.contributor.author | Louzada, S | ko |
dc.contributor.author | An, Y | ko |
dc.contributor.author | Kim, SY | ko |
dc.contributor.author | Kim, S | ko |
dc.contributor.author | Youk, Jeonghwan | ko |
dc.contributor.author | Park, S | ko |
dc.contributor.author | Koo, SH | ko |
dc.contributor.author | Keam, B | ko |
dc.contributor.author | Jeon, YK | ko |
dc.contributor.author | Ku, JL | ko |
dc.contributor.author | Yang, F | ko |
dc.contributor.author | Kim, TM | ko |
dc.contributor.author | Ju, Youngseok | ko |
dc.date.accessioned | 2017-04-17T07:26:15Z | - |
dc.date.available | 2017-04-17T07:26:15Z | - |
dc.date.created | 2017-03-28 | - |
dc.date.created | 2017-03-28 | - |
dc.date.issued | 2017-04 | - |
dc.identifier.citation | ANNALS OF ONCOLOGY, v.28, no.4, pp.890 - 897 | - |
dc.identifier.issn | 0923-7534 | - |
dc.identifier.uri | http://hdl.handle.net/10203/223230 | - |
dc.description.abstract | Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes. Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15; 19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominantmolecular clock-like signatures in all three cases (accounting for 54% = 75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells. Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs. | - |
dc.language | English | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.subject | MUTATIONAL PROCESSES | - |
dc.subject | THYMIC CARCINOMA | - |
dc.subject | BRD-NUT | - |
dc.subject | CANCER | - |
dc.subject | CELLS | - |
dc.subject | DIFFERENTIATION | - |
dc.subject | ABNORMALITY | - |
dc.subject | ONCOPROTEIN | - |
dc.subject | SIGNATURES | - |
dc.subject | MECHANISM | - |
dc.title | Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma | - |
dc.type | Article | - |
dc.identifier.wosid | 000397622100036 | - |
dc.identifier.scopusid | 2-s2.0-85019068452 | - |
dc.type.rims | ART | - |
dc.citation.volume | 28 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 890 | - |
dc.citation.endingpage | 897 | - |
dc.citation.publicationname | ANNALS OF ONCOLOGY | - |
dc.identifier.doi | 10.1093/annonc/mdw686 | - |
dc.contributor.localauthor | Ju, Youngseok | - |
dc.contributor.nonIdAuthor | Louzada, S | - |
dc.contributor.nonIdAuthor | An, Y | - |
dc.contributor.nonIdAuthor | Kim, SY | - |
dc.contributor.nonIdAuthor | Kim, S | - |
dc.contributor.nonIdAuthor | Park, S | - |
dc.contributor.nonIdAuthor | Koo, SH | - |
dc.contributor.nonIdAuthor | Keam, B | - |
dc.contributor.nonIdAuthor | Jeon, YK | - |
dc.contributor.nonIdAuthor | Ku, JL | - |
dc.contributor.nonIdAuthor | Yang, F | - |
dc.contributor.nonIdAuthor | Kim, TM | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | NUT midline carcinoma | - |
dc.subject.keywordAuthor | chromoplexy | - |
dc.subject.keywordAuthor | complex genomic rearrangement | - |
dc.subject.keywordAuthor | mutational signature | - |
dc.subject.keywordAuthor | bromodomain and extra terminal | - |
dc.subject.keywordPlus | MUTATIONAL PROCESSES | - |
dc.subject.keywordPlus | THYMIC CARCINOMA | - |
dc.subject.keywordPlus | BRD-NUT | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | ABNORMALITY | - |
dc.subject.keywordPlus | ONCOPROTEIN | - |
dc.subject.keywordPlus | SIGNATURES | - |
dc.subject.keywordPlus | MECHANISM | - |
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