Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Mod Pathol. 2016 Nov;29(11):1415-1423. doi: 10.1038/modpathol.2016.129. Epub 2016 Jul 29.
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.
胃肠道的平滑肌瘤主要发生在食管、胃和结肠。关于它们的遗传信息非常有限，尚未描述融合基因。我们在此介绍了在食管和小肠中发现的两个胃肠道平滑肌瘤的细胞遗传学和分子遗传学分析。食管平滑肌瘤的核型为 45，Y，der(X)t(X；6)(p22；p21)，inv(2)(p23q35)，add(6)(p21)，-11[cp6]/46，XY[7]。小肠平滑肌瘤的核型为 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 测序在两个肿瘤中均检测到 FN1-ALK 融合转录本。RT-PCR 联合 Sanger 测序验证了 FN1-ALK 融合转录本的存在。使用 ALK 断裂探针的荧光原位杂交进一步证实了 ALK 基因的重排。小肠平滑肌瘤中 ALK 的免疫组织化学研究显示，肿瘤细胞中存在阳性的强颗粒细胞质染色。这是首次在胃肠道平滑肌瘤中报道 ALK 融合。我们的研究结果具有潜在的临床意义，因为选择性 ALK 抑制剂克唑替尼在肿瘤携带 ALK 重排的患者中显示出疗效。因此，ALK 成为包括胃肠道平滑肌瘤在内的肿瘤携带 ALK 融合的患者的潜在治疗靶点。
