Genomic structure of the different translocations and resulting open reading frames. The upper panel shows the results for the ALL case, the lower panel for the CML case. On top of each panel the genomic structure of the junction fragment is shown. The ETV6 gene is represented by a thin line, the JAK2 gene by a thick line, and a fragment of unknown origin by an open bar. The boxes show the different exons. The sequence of the breakpoints is shown on top of the genomic structure. In the ALL case ETV6 genomic sequences are shown in capitals, JAK2 sequences in lowercase. Two splice variants are observed, the first fusing exon 4 of ETV6 to exon 16 of JAK2. The second splices exon 4 to exon 17 of JAK2. In the CML case exon 5 of ETV6 is spliced either to an exon (U) in the sequence of unknown origin which is then spliced to a cryptic acceptor site within exon 11 of JAK2 or directly to exon 12 of JAK2. ETV6 and JAK2 genomic sequences are indicated in uppercase letters, and a genomic sequence of unknown origin in lowercase letters. Splice donor and acceptor sites for the exon within this sequence are in boldface type. The composition of the fusion proteins encoded by the different splice variants is shown with the sequence of the junction fragments underneath. Arrows indicate the breakpoints. E, EcoRI site; HLH, oligomerization domain of ETV6; JH2, pseudokinase domain of JAK2; PTK, protein tyrosine kinase domain of JAK2.