Anaplastic lymphoma kinase (ALK) Gene Rearrangement in Children and Young Adults with Mesothelioma.
Journal of Thoracic Oncology 2019 November 26 [Link]
Mian I, Abdullaev Z, Morrow B, Kaplan RN, Gao S, Mettienen M, Schrump DS, Zgonc V, Wei JS, Khan J, Pack S, Hassan R
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 (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.
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.
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.