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M. Zaliova et al.
monoallelic ERGdel led to cell death.16 Even though, in the absence of a single cell analysis, we cannot exclude the possibility that one dominant ERGdel (detectable by SNP array) is accompanied in small subclones by another ERGdel present on the second allele (e.g. in patients UPN- 025, UPN-099) (Figure 4), taken together, our data clearly demonstrate the predominance of the polyclonal ERGdel pattern and the late origin of this lesion during leukemo- genesis in the majority of cases.
To conclude, the ERG gene deletion represents a unique aberration among all the other recurrent genetic changes that have been described in ALL so far. We show here that it is predominantly polyclonal, most likely a passenger aberration whose presence, however, potentially stratifies DUX4r-ALL into two subsets that differ in their genomic profile and outcome. Since it is frequently present at sub- clonal levels below the sensitivity of SNP
array/aCGH/MLPA, only genomic PCR or AmpliSeq should be used for ERGdel screening in order to appropri- ately define this subgroup and assess the IKZF1plus geno- type. The methods used to detect ERGdel differ signifi- cantly in sensitivity and this should also be taken into consideration when comparing and interpreting the find- ings of individual studies.
Acknowledgments
This study was supported by grants from the Czech Science Foundation (GJ15-06049Y), Charles University (Primus/MED/28) and the Czech Health Research Council (NV15-30626A), by the Ministry of Education, Youth and Sports (NPU I nr. LO1604 and LM2015091) and by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (University Hospital Motol, Prague, Czech Republic).
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