Pérot Gaëlle, Soubeyran Isabelle, Ribeiro Agnès, Bonhomme Benjamin, Savagner Frédérique, Boutet-Bouzamondo Nathalie, Hostein Isabelle, Bonichon Françoise, Godbert Yann, Chibon Frédéric
Department of Biopathology, Institut Bergonié, Bordeaux, France ; INSERM U916, Institut Bergonié, Bordeaux, France.
Department of Biopathology, Institut Bergonié, Bordeaux, France.
PLoS One. 2014 Jan 27;9(1):e87170. doi: 10.1371/journal.pone.0087170. eCollection 2014.
Thyroid carcinoma is the most common endocrine malignant tumor and accounts for 1% of all new malignant diseases. Among all types and subtypes of thyroid cancers that have been described so far, papillary thyroid carcinoma is the most frequent. The standard management treatment of these tumors consists of surgery, followed by radioiodine treatment in case of high risk of relapse. The most aggressive forms are commonly treated by chemotherapy, radiotherapy or experimental drug testing. We recently reported the case of a patient presenting an anaplastic thyroid carcinoma with lung metastases. Fluorescence in situ hybridization analysis allowed us to detect a rearrangement of the anaplastic lymphoma kinase (ALK) gene in both tumors. The patient was treated with crizotinib and presented an excellent drug response. We present here the subsequent investigations carried out to further characterize this genetic alteration and to assess the prevalence of ALK rearrangements in thyroid lesions. High resolution array-comparative genomic hybridization data complemented by RT-PCR and sequencing analyses, allowed us to demonstrate the presence of a STRN/ALK fusion. The STRN/ALK transcript consisted of the fusion between exon 3 of STRN and exon 20 of ALK. Subsequent screening of 75 various thyroid tumors by RT-PCR revealed that 2 out of 29 papillary thyroid carcinomas exhibited the same fusion transcript. None was detected in other types of malignant or benign thyroid lesions analyzed. These findings could pave the way for the development of new targeted therapeutic strategies in the treatment of papillary thyroid carcinomas and point to ALK inhibitors as promising agents that merit rapid evaluation.
甲状腺癌是最常见的内分泌恶性肿瘤，占所有新发恶性疾病的1%。在迄今为止描述的所有甲状腺癌类型和亚型中，乳头状甲状腺癌最为常见。这些肿瘤的标准治疗方法包括手术，若复发风险高则随后进行放射性碘治疗。最具侵袭性的类型通常采用化疗、放疗或实验性药物测试进行治疗。我们最近报告了一例患有间变性甲状腺癌并伴有肺转移的患者。荧光原位杂交分析使我们能够在两个肿瘤中检测到间变性淋巴瘤激酶（ALK）基因的重排。该患者接受了克唑替尼治疗，药物反应良好。我们在此展示随后进行的进一步研究，以更深入地表征这种基因改变，并评估甲状腺病变中ALK重排的发生率。通过高分辨率阵列比较基因组杂交数据，并辅以RT-PCR和测序分析，我们能够证明存在STRN/ALK融合。STRN/ALK转录本由STRN的第3外显子与ALK的第20外显子融合而成。随后通过RT-PCR对75种不同的甲状腺肿瘤进行筛查，结果显示29例乳头状甲状腺癌中有2例表现出相同的融合转录本。在分析的其他类型恶性或良性甲状腺病变中均未检测到。这些发现可能为乳头状甲状腺癌新的靶向治疗策略的开发铺平道路，并表明ALK抑制剂是值得快速评估的有前景药物。
