年轻间皮瘤病人的ALK突变情况

来源：知识城邦 多喝热水

　　间变淋巴瘤激酶（ALK）基因重排与儿童和青年间皮瘤的关系

结论

　　对于年轻的间皮瘤患者，应该评估是否存在ALK基因移位。

　　FISH可用来评估这种易位的存在，这些患者可能从靶向ALK的酪氨酸激酶抑制剂中获益。

　　Young patients with peritoneal mesothelioma should be evaluated for the presence of ALK translocations. Presence of this translocation should be assessed by FISH and these patients could potentially benefit from tyrosine kinase inhibitors targeting ALK.

背景

　　儿童和年轻人被诊断为恶性间皮瘤可能有独特的遗传特征。

　　在这项研究中，我们评估了间变性淋巴瘤激酶（ALK）在这些患者中的存在。

　　Children and young adults diagnosed with malignant mesothelioma may have unique genetic characteristics. In this study, we evaluated for the presence of the anaplastic lymphoma kinase (ALK) translocations in these patients.

方法

　　在间皮瘤自然史（MNH）（ClinicalTrials.gov编号NCT01950572）的前瞻性研究中，我们评估了40岁以下的患者是否存在ALK移位，而与疾病部位无关。

　　通过荧光原位杂交（FISH）评估这种易位的存在。如果阳性，则对肿瘤标本进行免疫组织化学（IHC）和RNA序列测定（RNASeq）。

　　In a prospective study of mesothelioma natural history (MNH) (ClinicalTrials.gov number NCT01950572) we assessed for the presence of the ALK translocation in patients less than 40 years old, irrespective of site of disease. The presence of this translocation was assessed via fluorescence in-situ hybridization (FISH). If positive, both immunohistochemistry (IHC) and RNA sequencing (RNASeq) were performed on the tumor specimen.

结果

　　2013年9月至2018年12月，共有373名患者参加了MNH研究，其中32名患者在诊断间皮瘤时年龄<40岁。

　　腹膜25例，胸膜5例，心包1例，双室间皮瘤1例。

　　32例间皮瘤患者中有2例（6%）出现了由FISH引起的ALK易位。

　　两名患者，一名14岁女性和一名27岁男性，均患有腹膜间皮瘤，均无石棉接触史、既往放射史或易感生殖系突变史。

　　IHC均未检测到ALK的表达。

　　RNAseq显示女性患者中存在一个STRN融合伴侣，但未能识别男性患者中的任何融合蛋白。

　　Between September 2013 and December 2018, 373 patients were enrolled on the MNH study of which 32 patients were <40 years old at the time of their mesothelioma diagnosis. 25 patients had peritoneal, 5 pleural, 1 pericardial and 1 had bi-compartmental mesothelioma. Presence of an ALK translocation by FISH was seen in 2 of the 32 (6%) mesothelioma patients. Both patients, a 14 year old female and a 27 year old male, had peritoneal mesothelioma and neither had history of asbestos exposure, prior radiation or predisposing germline mutations. Neither had detectable ALK expression by IHC. RNAseq revealed the presence of an STRN fusion partner in the female patient but failed to identify any fusion protein in the male patient.