Case Report: Whole genome sequencing identifies CCDC88C as a novel JAK2 fusion partner in pediatric T-cell acute lymphoblastic leukemia

Abstract

In the present report, we applied whole genome sequencing (WGS) to genetically characterize a case of pediatric T-cell acute lymphoblastic leukemia (ALL) refractory to standard therapy. WGS identified a novel JAK2 fusion, with CCDC88C as a partner. CCDC88C encodes a protein part of the Wnt signaling pathway and has previously been described in hematological malignancies as fusion partner to FLT3 and PDGFRB. The novel CCDC88C::JAK2 fusion gene results in a fusion transcript, predicted to produce a hybrid protein, which retains the kinase domain of JAK2 and is expected to respond to JAK2 inhibitors. This report illustrates the potential of WGS in the diagnostic setting of ALL.

Keywords: JAK2 fusions; pediatric T-ALL; precision medicine; targeted therapy; whole genome sequencing.

Figure 1

(A) Circos plot showing chromosomes 9 and 14; the black lines represent the reciprocal translocation together with the concomitant inversion of the small fragment from 9p23.1 (red line). (B) Aberrant metaphase hybridized with JAK2 break apart probe (red/green signal, CytoTest) and 14 centromere probe (blue signal) showing the distal red signal (5′ end) of JAK2 translocated to 14q.

Figure 2

Cartoon showing a schematic representation of chromosomes 9 (blue) and 14 (yellow) at the derivative chromosomes 9 and 14 (upper panel), the black squares mark the junctions. Middle cartoon represents a blow up of the junctions illustrating the creation of the fusion gene on derivative chromosome 9 (der9). The lower panel represents a magnification of the fusion gene showing exons 1–25 in CCDC88C joined to exons 16–25 in JAK2.