Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
J Thorac Oncol. 2020 Mar;15(3):457-461. doi: 10.1016/j.jtho.2019.11.011. Epub 2019 Nov 26.
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.
In a prospective study of mesothelioma natural history (ClinicalTrials.gov number NCT01950572), we assessed for the presence of the ALK translocation in patients younger than 40 years, irrespective of the site of disease. The presence of this translocation was assessed by means of fluorescence in situ hybridization (FISH). If the patients tested positive for the ALK translocation, both immunohistochemistry and RNA sequencing were performed on the tumor specimen.
Between September 2013 and December 2018, 373 patients were enrolled in the mesothelioma natural history study, of which 32 patients were 40 years old or younger at the time of their mesothelioma diagnosis. There were 25 patients with peritoneal mesothelioma, five with pleural mesothelioma, one with pericardial mesothelioma, and one with bicompartmental mesothelioma. Presence of an ALK translocation by FISH was seen in two of the 32 patients (6%) with mesothelioma. Both patients, a 14-year-old female and a 27-year-old male, had peritoneal mesothelioma and had no history of asbestos exposure, prior radiation therapy, or predisposing germline mutations. Neither had detectable ALK expression by immunohistochemistry. RNA sequencing revealed the presence of an STRN fusion partner in the female patient but failed to identify any fusion protein in the male patient.
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.
诊断为恶性间皮瘤的儿童和青少年可能具有独特的遗传特征。在这项研究中，我们评估了这些患者中是否存在间变性淋巴瘤激酶（ALK）易位。
在一项间皮瘤自然史的前瞻性研究（ClinicalTrials.gov 编号 NCT01950572）中，我们评估了年龄在 40 岁以下的患者是否存在 ALK 易位，无论疾病部位如何。通过荧光原位杂交（FISH）评估该易位的存在。如果患者的 ALK 易位检测为阳性，则对肿瘤标本进行免疫组织化学和 RNA 测序。
2013 年 9 月至 2018 年 12 月，共有 373 名患者入组间皮瘤自然史研究，其中 32 名患者在诊断为间皮瘤时年龄在 40 岁或以下。25 名患者患有腹膜间皮瘤，5 名患有胸膜间皮瘤，1 名患有心包间皮瘤，1 名患有双腔间皮瘤。通过 FISH 检测到 32 名间皮瘤患者中有 2 名（6%）存在 ALK 易位。这两名患者均为女性（14 岁）和男性（27 岁），患有腹膜间皮瘤，没有石棉暴露史、既往放疗史或致病变异的种系突变。两者的免疫组织化学均未检测到 ALK 表达。RNA 测序显示女性患者存在 STRN 融合伙伴，但在男性患者中未发现任何融合蛋白。
患有腹膜间皮瘤的年轻患者应评估 ALK 易位的存在。该易位的存在应通过 FISH 进行评估，这些患者可能受益于针对 ALK 的酪氨酸激酶抑制剂。
