Figure 4

Fusion transcript and genomic DNA sequencing of the breakpoint in recurrent metastatic lung inflammatory myofibroblastic tumor (from 2002). (A) Chromatogram showing the sequence of CARS-ALK fusion transcript at the breakpoint. The CARS sequence at the 5′ portion of the transcript (left) is followed by the ALK sequence at the 3′ portion (right). Lower line shows the transcription of the fusion. Note the last nucleotide of the CARS portion of the sequence (G) contributes to the GTG triplet encoding Valine (underlined), maintaining the in-frame translation of the ALK catalytic domain at the C terminus of the predicted chimeric protein. (B) The scheme and chromatogram showing the genomic breakpoint of the hybrid CARS-ALK gene. The genomic DNA was amplified with the primers located in intronic sequences flanking the fused exons of both genes (thick arrows). The resulting 1760-bp fragment was cloned and sequenced. The chromatogram shows the portion of the intronic hybrid sequence in the proximity of the breakpoint. Two nucleotides at the intronic junction (AT) are identical in both fused genes and might be contributed by either of them.