Recurrent fusion of the genes FN1 and ALK in gastrointestinal leiomyomas

Leiomyomas of the gastrointestinal tract are mostly found in the esophagus, stomach, and colon. Genetic information about them is very limited and no fusion genes have been described. We present herein cytogenetic and molecular genetic analyses of two gastrointestinal leiomyomas found in the esophagus and small intestine. The esophageal leiomyoma had the karyotype 45,Y,der(X)t(X;6)(p22;p21),inv(2)(p23q35),add(6)(p21), - 11[cp6]/46, XY[7]. The intestinal leiomyoma karyotype was 46,X,add(X)(q2?),der(2)add(2)(p23)add(2)(q33),add(4)(p14), add(14)(q22)[10]/47,XX,+12[2]/46,XX[1]. RNA-sequencing detected FN1-ALK fusion transcripts in both tumors. RT-PCR together with Sanger sequencing verified the presence of the FN1-ALK fusion transcripts. Fluorescence in situ hybridization using an ALK breakapart probe further confirmed the rearrangement of the ALK gene. Immunohistochemical investigation of ALK in the leiomyoma of the small intestine revealed positivity with strong granular cytoplasmatic staining in the tumor cells. This is the first ever ALK fusion reported in gastrointestinal leiomyomas. Our results are of potential clinical importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients whose tumors harbor ALK rearrangements. Thus, ALK emerges as a possible therapeutic target in patients whose tumors, including gastrointestinal leiomyomas, carry ALK fusions.