@article{Marketa Zaliova_Eliska Potuckova_Lenka Hovorkova_Alena Musilova_Lucie Winkowska_Karel Fiser_Jan Stuchly_Ester Mejstrikova_Julia Starkova_Jan Zuna_Jan Stary_Jan Trka_2019, place={Pavia, Italy}, title={ERG deletions in childhood acute lymphoblastic leukemia with DUX4 rearrangements are mostly polyclonal, prognostically relevant and their detection rate strongly depends on screening method sensitivity}, volume={104}, url={https://haematologica.org/article/view/8971}, DOI={10.3324/haematol.2018.204487}, abstractNote={<em>ERG</em>-deletions occur recurrently in acute lymphoblastic leukemia, especially in the <em>DUX4</em>-rearranged subtype. The <em>ERG</em>-deletion was shown to positively impact prognosis of patients with <em>IKZF1</em>-deletion and its presence precludes assignment into <em>IKZF1</em><sup>plus</sup> group, a novel high-risk category on AIEOP-BFM ALL trials. We analyzed the impact of different methods on <em>ERG</em>-deletion detection rate, evaluated <em>ERG</em>-deletion as a potential marker for <em>DUX4</em>-rearranged leukemia, studied its associations with molecular and clinical characteristics within this leukemia subtype, and analyzed its clonality. Using single-nucleotide-polymorphism array, genomic polymerase chain reaction (PCR) and amplicon-sequencing we found <em>ERG</em>-deletion in 34% (16 of 47), 66% (33 of 50) and 78% (39 of 50) of <em>DUX4</em>-rearranged leukemia, respectively. False negativity of <em>ERG</em>-deletion by single-nucleotide-polymorphism array caused <em>IKZF1</em><sup>plus</sup> misclassification in 5 patients. No <em>ERG</em>-deletion was found outside the <em>DUX4</em>-rearranged cases. Within <em>DUX4</em>-rearranged leukemia, the <em>ERG</em>-deletion was associated with higher total number of copy-number aberrations, and, importantly, the <em>ERG</em>-deletion positivity by PCR was associated with better outcome [5-year event-free survival (EFS), <em>ERG</em>-deletion-positive 93% <em>vs. ERG</em>-deletion-negative 68%, <em>P</em>=0.022; 5-year overall survival (OS), <em>ERG</em>-deletion-positive 97% <em>vs. ERG</em>-deletion-negative 75%, <em>P</em>=0.029]. Ultra-deep amplicon-sequencing revealed distinct co-existing <em>ERG</em>-deletions in 22 of 24 patients. In conclusion, our data demonstrate inadequate sensitivity of single-nucleotide-polymorphism array for <em>ERG</em>-deletion detection, unacceptable for proper <em>IKZF1</em><sup>plus</sup> classification. Even using more sensitive methods (PCR/amplicon-sequencing) for its detection, <em>ERG</em>-deletion is absent in 22-34% of <em>DUX4</em>-rearranged leukemia and does not represent an adequately sensitive marker of this leukemia subtype. Importantly, the <em>ERG</em>-deletion potentially stratifies the <em>DUX4</em>-rearranged leukemia into biologically/clinically distinct subsets. Frequent polyclonal pattern of <em>ERG</em&gt;-deletions shows that late origin of this lesion is more common than has been previously described.}, number={7}, journal={Haematologica}, author={Marketa Zaliova and Eliska Potuckova and Lenka Hovorkova and Alena Musilova and Lucie Winkowska and Karel Fiser and Jan Stuchly and Ester Mejstrikova and Julia Starkova and Jan Zuna and Jan Stary and Jan Trka}, year={2019}, month={Jun.}, pages={1407-1416} }