A novel fusion between CDC42BPB and ALK in a patient with quadruple wild-type gastrointestinal stromal tumor

Background: Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in gastrointestinal tract, with striking features of morphology and immunohistochemistry. But GISTs in pregnancy could seldom be found. Pathogenic activating mutations of the proto-oncogene KIT and PDGFRA are detected in majority GISTs, and adjuvant imatinib therapy targeting KIT and PDGFRA mutations is recommended for patients with high-risk GIST. However, some rare subgroups with distinct molecular features remain uncovered and more therapeutic targets need to be revealed.

Methods: The DNA/RNA samples were detected using the NGS-based YuanSu450 gene panel. After identifying the CDC42BPB-ALK fusion by NGS, this novel fusion was further confirmed by Sanger sequencing. Subsequently, FISH analysis was performed using the Vysis ALK Break Apart FISH Probe kit to testify the ALK status. ALK protein expression was confirmed by IHC (D5F3 and 5A4).

Results: Herein, we reported the first case of quadruple wild-type (WT) GIST with ALK-CDC42BPB fusion and ALK (D5F3) overexpression. In this study, we described a 33-year-old pregnant patient in lactation who had a massive space occupying lesion (with the maximum diameter of 22 cm) in the stomach and was eventually diagnosed as quadruple WT GIST (KIT^WT /PDGFRA^WT /SDH^WT /RAS-P^WT ).

Conclusion: We unexpectedly found that this GIST patient showed ALK (D5F3) overexpression and harbored a novel fusion CDC42BPB exon 24-ALK in exon 20.