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Acute Leukemias

The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial

Leukemia volume 25, pages 622–628 (2011)Cite this article

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Abstract

The dic(9;20)(p13.2;q11.2) is reported to be present in ∼2% of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). However, it easily escapes detection by G-banding analysis and its true prevalence is hence unknown. We performed interphase fluorescence in situ hybridization analyses—in a three-step manner—using probes for: (i) CDKN2A at 9p21, (ii) 20p and 20q subtelomeres and (iii) cen9 and cen20. Out of 1033 BCP ALLs diagnosed from 2001 to 2006, 533 were analyzed; 16% (84/533) displayed 9p21 deletions, of which 30% (25/84) had dic(9;20). Thus, dic(9;20)-positivity was found in 4.7% (25/533), making it the third most common genetic subgroup after high hyperdiploidy and t(12;21)(p13;q22). The dic(9;20) was associated with a female predominance and an age peak at 3 years; 18/25 (72%) were allocated to non-standard risk treatment at diagnosis. Including cases detected by G-banding alone, 29 dic(9;20)-positive cases were treated according to the NOPHO ALL 2000 protocol. Relapses occurred in 24% (7/29) resulting in a 5-year event-free survival of 0.69, which was significantly worse than for t(12;21) (0.87; P=0.002) and high hyperdiploidy (0.82; P=0.04). We conclude that dic(9;20) is twice as common as previously surmised, with many cases going undetected by G-banding analysis, and that dic(9;20) should be considered a non-standard risk abnormality.

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Acknowledgements

We thank Sigrid Sahlén for excellent technical assistance and all colleagues in the Nordic Society of Paediatric Haematology and Oncology who provided patient samples. This work was supported by grants from the Swedish Childhood Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, Karolinska Institutet, the Mary Béve Foundation for Pediatric Cancer Research and Henning, and Ida Persson Foundation.

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Authors and Affiliations

  1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    V Zachariadis, F Gauffin, E Kuchinskaya, J Schoumans, E Blennow, G Barbany, M Nordenskjöld & A Nordgren

  2. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden

    F Gauffin & B Gustafsson

  3. Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden

    M Heyman

  4. Department of Medical Biosciences, Medical and Clinical Genetics, University of Umeå, Umeå, Sweden

    I Golovleva

  5. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

    H Ehrencrona & L Cavelier

  6. Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden

    L Palmqvist

  7. Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden

    G Lönnerholm

  8. Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden

    B Johansson

  9. Department of Clinical Sciences, Pediatrics, University of Umeå, Umeå, Sweden

    E Forestier

  10. Department of Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    J Schoumans

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  1. V Zachariadis
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for the Nordic Society of Pediatric Hematology, Oncology (NOPHO) and the Swedish Cytogenetic Leukemia Study Group (SCLSG)

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Correspondence to E Forestier or A Nordgren.

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Author contributions

VZ performed research, analyzed data and wrote the paper. FG performed research and analyzed data. EK and JS performed research. MH identified specimens, provided clinical data, and analyzed data. GL, EB, GB, IG, BG, HE, LC, MN and LP analyzed data. EF and BJ analyzed data and wrote the paper. AN, principal investigator, designed research, analyzed data and wrote the paper.

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Zachariadis, V., Gauffin, F., Kuchinskaya, E. et al. The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial. Leukemia 25, 622–628 (2011). https://doi.org/10.1038/leu.2010.318

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