Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney

Angshumoy Roy, Vijetha Kumar, Barry Zorman, Erica Fang, Katherine M. Haines, HarshaVardhan Doddapaneni, Oliver A. Hampton, Simon White, Abhishek A. Bavle, Nimesh R. Patel, Karen W. Eldin, M. John Hicks, Dinesh Rakheja, Patrick J Leavey, Stephen X Skapek, James F Amatruda, Jed G. Nuchtern, Murali M. Chintagumpala, David A. Wheeler, Sharon E. PlonPavel Sumazin, D. Williams Parsons

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of 27 (85%) pediatric clear cell sarcomas of the kidney (CCSK) from two independent cohorts. We profile CCSK tumours using a combination of whole-exome, transcriptome and targeted sequencing. Identical ITD mutations are found in primary and relapsed tumour pairs but not in adjacent normal kidney or blood. Mutant BCOR transcripts and proteins are markedly upregulated in ITD-positive tumours. Transcriptome analysis of ITD-positive CCSKs reveals enrichment for PRC2-regulated genes and similarity to undifferentiated sarcomas harbouring BCOR-CCNB3 fusions. The discovery of recurrent BCOR ITDs defines a major oncogenic event in this childhood sarcoma with significant implications for diagnostic and therapeutic approaches to this tumour.

Original languageEnglish (US)
Article number8891
JournalNature Communications
Volume6
DOIs
StatePublished - Nov 17 2015

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Clear Cell Sarcoma
Co-Repressor Proteins
kidneys
cancer
Tumors
Kidney
tumors
cells
Neoplasms
Sarcoma
genes
Genes
Exome
Pediatrics
sequencing
Gene Expression Profiling
mutations
Transcriptome
blood
Cluster Analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Roy, A., Kumar, V., Zorman, B., Fang, E., Haines, K. M., Doddapaneni, H., ... Parsons, D. W. (2015). Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nature Communications, 6, [8891]. https://doi.org/10.1038/ncomms9891

Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. / Roy, Angshumoy; Kumar, Vijetha; Zorman, Barry; Fang, Erica; Haines, Katherine M.; Doddapaneni, HarshaVardhan; Hampton, Oliver A.; White, Simon; Bavle, Abhishek A.; Patel, Nimesh R.; Eldin, Karen W.; John Hicks, M.; Rakheja, Dinesh; Leavey, Patrick J; Skapek, Stephen X; Amatruda, James F; Nuchtern, Jed G.; Chintagumpala, Murali M.; Wheeler, David A.; Plon, Sharon E.; Sumazin, Pavel; Parsons, D. Williams.

In: Nature Communications, Vol. 6, 8891, 17.11.2015.

Research output: Contribution to journalArticle

Roy, A, Kumar, V, Zorman, B, Fang, E, Haines, KM, Doddapaneni, H, Hampton, OA, White, S, Bavle, AA, Patel, NR, Eldin, KW, John Hicks, M, Rakheja, D, Leavey, PJ, Skapek, SX, Amatruda, JF, Nuchtern, JG, Chintagumpala, MM, Wheeler, DA, Plon, SE, Sumazin, P & Parsons, DW 2015, 'Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney', Nature Communications, vol. 6, 8891. https://doi.org/10.1038/ncomms9891
Roy, Angshumoy ; Kumar, Vijetha ; Zorman, Barry ; Fang, Erica ; Haines, Katherine M. ; Doddapaneni, HarshaVardhan ; Hampton, Oliver A. ; White, Simon ; Bavle, Abhishek A. ; Patel, Nimesh R. ; Eldin, Karen W. ; John Hicks, M. ; Rakheja, Dinesh ; Leavey, Patrick J ; Skapek, Stephen X ; Amatruda, James F ; Nuchtern, Jed G. ; Chintagumpala, Murali M. ; Wheeler, David A. ; Plon, Sharon E. ; Sumazin, Pavel ; Parsons, D. Williams. / Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. In: Nature Communications. 2015 ; Vol. 6.
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abstract = "The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of 27 (85{\%}) pediatric clear cell sarcomas of the kidney (CCSK) from two independent cohorts. We profile CCSK tumours using a combination of whole-exome, transcriptome and targeted sequencing. Identical ITD mutations are found in primary and relapsed tumour pairs but not in adjacent normal kidney or blood. Mutant BCOR transcripts and proteins are markedly upregulated in ITD-positive tumours. Transcriptome analysis of ITD-positive CCSKs reveals enrichment for PRC2-regulated genes and similarity to undifferentiated sarcomas harbouring BCOR-CCNB3 fusions. The discovery of recurrent BCOR ITDs defines a major oncogenic event in this childhood sarcoma with significant implications for diagnostic and therapeutic approaches to this tumour.",
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