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Detecting dic(9;20)(p13.2;p11.2)-positive B-cell precursor acute lymphoblastic leukemia in a clinical setting using fluorescence in situ hybridization

Leukemia volume 28, pages 196–198 (2014)Cite this article

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The dic(9;20)(p13.2;p11.2) is a recurrent chromosomal aberration in childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL). While it is at present unclear whether dic(9;20) should be considered a primary aberration or not, the majority of dic(9;20)-positive cases clearly lack other prognostically important and risk-stratifying chromosomal abnormalities.1, 2, 3, 4 Treated according to the Nordic NOPHO ALL-2000 protocol, dic(9;20)-positive pediatric ALL is associated with a significantly higher risk of relapse compared with other standard risk aberrations, such as t(12;21)(p13;q22) and high hyperdiploidy, suggesting that dic(9;20) should be considered a nonstandard risk abnormality. The dic(9;20) translocation is present in up to 5% of childhood BCP ALL; however, it easily escapes detection by traditional cytogenetic approaches because of the subtle nature of the aberration.1 We have previously described a three-step approach to detect dic(9;20) using interphase fluorescence in situ hybridization (FISH), utilizing the unbalanced nature of the rearrangement, to identify, in a sequential order, the 9p21 deletions, 20p/20q imbalances and co-localization of centromeres 9 and 20 associated with dic(9;20).1 However, in our further experience, this approach is impractical for clinical use. Hence, at present, a reliable and cost-effective method for detecting dic(9;20)-positive ALL is lacking. Herein we describe the design and the validation of a three-color FISH probe kit for identifying dic(9;20) in a routine laboratory setting.

Previous methods for detecting dic(9;20) have relied heavily on karyotyping, often using monosomy 20 as a marker for the aberration.5 However, a considerable subset of dic(9;20)-positive cases has two normal chromosome 20 homologs in addition to the rearranged one and are consequently often not detected by chromosome banding alone.1 Genomic profiling using array-based techniques reveal the unbalanced nature of the dic(9;20) rearrangement, as a loss of chromosome arms 9p and 20q or 9p deletion and gain of 20p in cases with two normal chromosome 20 homologs, but cannot confirm the dicentric nature of the rearrangement.6, 7 There are ALLs with similar breakpoints and genomic imbalances that evidently lack dic(9;20) (Den Boer et al.8 and Nordgren, unpublished data), but it is not clear whether such cases are biologically and/or clinically distinct from dic(9;20)-positive ALLs. Furthermore, at present, only a few laboratories perform array analyses in routine diagnostics of ALLs. In addition, unlike genomic arrays, FISH can reliably be used to visualize dic(9;20) on metaphases and to detect samples with low-level mosaicism at diagnosis or during follow-up. For these reasons, we consider FISH to be the current method of choice for reliable detection of dic(9;20) in a routine clinical setting.

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References

  1. Zachariadis V, Gauffin F, Kuchinskaya E, Heyman M, Schoumans J, Blennow 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 2011; 25: 622–628.

    Article  CAS  PubMed  Google Scholar 

  2. Forestier E, Gauffin F, Andersen MK, Autio K, Borgström G, Golovleva I et al. Clinical and cytogenetic features of pediatric dic(9;20)(p13.2;q11.2)-positive B-cell precursor acute lymphoblastic leukemias: a Nordic series of 24 cases and review of the literature. Genes Chromosomes Cancer 2008; 47: 149–158.

    Article  CAS  PubMed  Google Scholar 

  3. Pichler H, Möricke A, Mann G, Teigler-Schlegel A, Niggli F, Nebral K et al. Prognostic relevance of dic(9;20)(p11;q13) in childhood B-cell precursor acute lymphoblastic leukaemia treated with Berlin-Frankfurt-Münster (BFM) protocols containing an intensive induction and post-induction consolidation therapy. Br J Haematol 2010; 149: 93–100.

    Article  CAS  PubMed  Google Scholar 

  4. Moorman AV, Ensor HM, Richards SM, Chilton L, Schwab C, Kinsey SE et al. Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol 2010; 11: 429–438.

    Article  CAS  PubMed  Google Scholar 

  5. Clark R, Byatt SA, Bennett CF, Brama M, Martineau M, Moorman AV et al. Monosomy 20 as a pointer to dicentric (9;20) in acute lymphoblastic leukemia. Leukemia 2000; 14: 241–246.

    Article  CAS  PubMed  Google Scholar 

  6. Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Stocking C, Sanada M et al. Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray. Proc Natl Acad Sci USA 2008; 105: 11921–11926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zachariadis V, Schoumans J, Barbany G, Heyman M, Forestier E, Johansson B et al. Homozygous deletions of CDKN2A are present in all dic(9;20)(p13·2;q11·2)-positive B-cell precursor acute lymphoblastic leukaemias and may be important for leukaemic transformation. Br J Haematol 2012; 159: 488–491.

    Article  CAS  PubMed  Google Scholar 

  8. Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 2009; 10: 125–134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mitelman F, Johansson B, Mertens F Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, 2012. http://cgap.nci.nih.gov/Chromosomes/Mitelman.

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Acknowledgements

This study was supported by grants from the Swedish Childhood Cancer Foundation, Karolinska Institutet, Mary Béve's foundation and Stockholm County Council. Kreatech Diagnostics produced and provided a limited number of FISH probe reagents free of charge.

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Authors and Affiliations

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

    V Zachariadis, I Öfverholm, G Barbany, M Nordenskjöld & A Nordgren

  2. Center of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

    V Zachariadis, I Öfverholm, G Barbany, M Nordenskjöld & A Nordgren

  3. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden

    V Zachariadis, I Öfverholm, G Barbany, E Halvardsson, M Nordenskjöld & A Nordgren

  4. Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    J Schoumans

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

    E Forestier

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

    B Johansson

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  1. V Zachariadis
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  2. J Schoumans
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  9. A Nordgren
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Correspondence to A Nordgren.

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Author contributions

VZ performed research, analyzed data and wrote the paper. EH performed laboratory work. IÖ, JS, GB, BJ and MN analyzed data. EF analyzed and provided clinical data. AN (principal investigator) designed research, analyzed data and wrote the paper.

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Zachariadis, V., Schoumans, J., Öfverholm, I. et al. Detecting dic(9;20)(p13.2;p11.2)-positive B-cell precursor acute lymphoblastic leukemia in a clinical setting using fluorescence in situ hybridization. Leukemia 28, 196–198 (2014). https://doi.org/10.1038/leu.2013.189

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