PMC5705803_01
Allele frequency comparison of 14 persistent mutations between diagnosis and 2nd relapse showed shift in CDKN2AR80* (A), evidently arising from copy neutral loss of heterozygosity involving a 33 million basepair stretch of chromosome 9, and thus not detected by array-CGH. Some deviation from the hypothetical frequency is expected, when performing exome sequencing, but the allele frequency distributions are in agreement with leukemic burden (B), where dominant clone and some subclonality at diagnose can be postulated from low resolution kernel density estimations (left). Only one distinct high frequency peak is detected at second relapse (right). The clonal pattern is supported by the mutations held in each peak, i.e. the persistent mutations (IKZF1, UNC3D etc.) are generally found in the dominant clone, whereas FLT3D835Y is located in the disappearing subclone. Frequency scatter plots (C, left) and kernel distribution estimation (C, right) demonstrated trisomy of chromosome 4 (C) at 2nd relapse and copy-number neutral loss of heterozygosity on chromosome 9 (D), when comparing to diagnosis.
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