PMC9871838_01
(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.
fped-10-1082986-g001.jpg
PMC9871838_01_fped-10-1082986-g001.jpg
F1
Two of these SVs affected the JAK2 locus on 9p24.1 and inspection in IGV revealed a shared breakpoint suggesting that both SVs had occurred in the same genomic rearrangement (Supplementary Figure 1). Both events are visualized in the Circos plot in Figure 1A. The rearrangement of JAK2 could be verified with metaphase FISH that confirmed that the 5' signal at the JAK2 locus was translocated to chromosome 14 while the 3' signal was retained on derivative chromosome 9 (Figure 1B).
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.
fped-10-1082986-g002.jpg
PMC9871838_01_fped-10-1082986-g002.jpg
F2
As a result of the inversion from the 9p fragment, the genes are arranged in opposite orientations and thus no reciprocal fusion is created at derivative 14 (Figure 2). According to the WGS findings, the rearrangement juxtaposes exons 1 to 25 of CCDC88C to exons 16 through 25 of JAK2, creating a novel fusion gene (Figure 2).