Blood Journal
Leading the way in experimental and clinical research in hematology

BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders

  1. Frederik Damm1,
  2. Virginie Chesnais2,
  3. Yasunobu Nagata3,
  4. Kenichi Yoshida3,
  5. Laurianne Scourzic4,
  6. Yusuke Okuno3,
  7. Raphael Itzykson5,
  8. Masashi Sanada3,
  9. Yuichi Shiraishi6,
  10. Véronique Gelsi-Boyer7,
  11. Aline Renneville8,
  12. Satoru Miyano9,
  13. Hiraku Mori10,
  14. Lee-Yung Shih11,
  15. Sophie Park12,
  16. François Dreyfus12,
  17. Agnes Guerci-Bresler12,
  18. Eric Solary13,
  19. Christian Rose14,
  20. Stéphane Cheze15,
  21. Thomas Prébet16,
  22. Norbert Vey16,
  23. Marion Legentil17,
  24. Yannis Duffourd18,
  25. Stéphane de Botton13,
  26. Claude Preudhomme19,
  27. Daniel Birnbaum20,
  28. Olivier A. Bernard4,
  29. Seishi Ogawa3,
  30. Michaela Fontenay21, and
  31. Olivier Kosmider21,*
  1. 1 Institut Gustave Roussy, VIllejuif, France;
  2. 2 Departement d'Immunologie et Hematologie, Institut Cochin, Paris, France;
  3. 3 Cancer Genomics Project, Graduate School of Medicine, Department of Pathology, The University of Tokyo, Tokyo, Japan;
  4. 4 INSERM, U985, Villejuif, France;
  5. 5 UMR 1009, Villejuif, France;
  6. 6 Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan;
  7. 7 Centre de Recherche en Cancerologie de Marseille, UMR1068 INSERM, Institut Paoli-Calmette, Marseille, France;
  8. 8 Laboratoire d'hematologie, CHRU Lille, France;
  9. 9 Laboratory of Sequence Data Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan;
  10. 10 Department of Hematology, Showa University, Tokyo, Japan;
  11. 11 Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Japan;
  12. 12 Unite Fonctionnelle d'hematologie clinique, Hopital Cochin, Paris, France;
  13. 13 Institut Gustave Roussy, Villejuif, France;
  14. 14 Service d'oncologie et d'hematologie, Hopital Saint Vincent de Paul, UC de Lille Universite Nord de France, Lille, France;
  15. 15 Service d'hematologie, CHRU, Caen, France;
  16. 16 Departement d'Hematologie, Institut Paoli-Calmettes, Marseille, France;
  17. 17 Institut Gustave Roussy - Plateforme de genomique, Villejuif, France;
  18. 18 Institut Gustave Roussy - Plateforme de Bioinformatique, Villejuif, France;
  19. 19 Laboratoire d'Hematologie, CHRU Lille, France;
  20. 20 Aix-Marseille Universite, France;
  21. 21 INSERM U1016, France
  1. * Corresponding author; email: olivier.kosmider{at}

Key points

  • Despite a low frequency BCOR mutations might be considered as a key gene in risk stratification.

  • Deep sequencing technologies show that BCOR mutations arise commonly after other concomitant mutations in MDS.


Patients with low-risk myelodysplastic syndromes (MDS) that rapidly progress to AML remain a challenge in disease management. Using whole-exome-sequencing of a MDS patient, we identified a somatic mutation in BCOR gene also mutated in AML. Sequencing of BCOR and related BCORL1 genes in a cohort of 354 MDS patients identified a total of 15 patients with inactivating BCOR mutations (15/354=4.2%) and 3 with BCORL1 mutations (3/354=0.8%). BCOR mutations were associated with RUNX1 (P=0.002) and DNMT3A mutations (P=0.015). Moreover, mutations of BCOR (4/54=7.4%) and BCORL1 (1/54=1.8%) were found in a cohort of 54 CMML, while BCORL1 mutations were found in 9.1% of 22 AML-MRC patients. Using deep sequencing, we show that BCOR mutations arise after mutations affecting genes involved in splicing machinery or epigenetic regulation. In univariate analysis, BCOR mutations were associated with poor prognosis in MDS (OS: P=0.013; cumulative incidence of AML transformation: P=0.005). Multivariate analysis including age, IPSS, transfusion dependence, ASXL1, CBL, RUNX1, TEL/ETV6, and TP53 mutation status confirmed a significant inferior OS to patients with BCOR mutation (HR: 3.3; 95%CI 1.4–8.1; P=0.008). These data suggest that BCOR mutations define the clinical course rather than disease initiation. Despite infrequent mutations, BCOR analyses should be considered in risk stratification.

  • Submitted November 27, 2012.
  • Accepted September 8, 2013.