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Characterizing chromosomal break points of t(12;21)[ETV6–RUNX1]-positive leukaemia using multiple tiling PCR on whole-genome-amplified DNA

Leukemia volume 24, pages 203–205 (2010)Cite this article

Childhood acute lymphoblastic leukaemia is frequently initiated prenatally with a subsequent latent period of several years.1 The most common subtype (20% of all cases) harbours the t(12;21)(p13;q22)[ETV6–RUNX1] translocation.2 Clone-specific ETV6–RUNX1 fusion primers have allowed the mapping of parts of the natural history of this acute lymphoblastic leukaemia subset, including back tracking to the neonatal period.3, 4 Although other markers have been used, the ETV6–RUNX1 translocation remains paramount in studies of the natural history of common childhood acute lymphoblastic leukaemia because of its relatively high incidence and its leukaemia specificity as opposed to, for example, antigen receptor markers.5 The clone-specific ETV6–RUNX1 break points have mainly been identified by multiplex PCR or by long-distance inverse PCR techniques.3, 4, 6, 7 However, because of the insufficient quantity and quality of diagnostic DNA and the spread of potential break points over almost 200 kb, these approaches may frequently fail, and thus hamper the exploration of ETV6–RUNX1-positive cases.

Whole-genome amplification (WGA) methods have been developed to overcome the quantity of DNA as a limiting factor in molecular genetics. Accordingly, we explored the usefulness of WGA in combination with a multiple tiling PCR setup on three potential DNA sources for the identification of ETV6–RUNX1 chromosomal break points.

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Acknowledgements

This study has received financial support from the Danish Childhood Cancer Foundation, from Michael Goldschmidt Holding A/S, and from the Danish Cancer Society (Grant no. DP06136). Kjeld Schmiegelow holds the Danish Childhood Cancer Foundation professorship in Paediatric Oncology.

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Authors and Affiliations

  1. Department of Pediatrics, The University Hospital Rigshospitalet, Copenhagen, Denmark

    U Lausten-Thomsen & K Schmiegelow

  2. Tissue Type Laboratory, The University Hospital Rigshospitalet, Copenhagen, Denmark

    H O Madsen

  3. Institute of Gynaecology, Obstetrics and Paediatrics, The Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

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  1. U Lausten-Thomsen
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  2. H O Madsen
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  3. K Schmiegelow
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Correspondence to K Schmiegelow.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Lausten-Thomsen, U., Madsen, H. & Schmiegelow, K. Characterizing chromosomal break points of t(12;21)[ETV6–RUNX1]-positive leukaemia using multiple tiling PCR on whole-genome-amplified DNA. Leukemia 24, 203–205 (2010). https://doi.org/10.1038/leu.2009.170

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