Molecular profiling of Chinese systemic anaplastic large cell lymphoma patients: novel evidence of genetic heterogeneity.

Background: Anaplastic large cell lymphoma (ALCL) is a rare non-Hodgkin lymphoma. A comprehensive understanding of the genetic and clinical heterogeneity of ALCL may help to improve the clinical management of patients with ALCL. However, due to the rarity of the disease, the genetic heterogeneity of ALCL has not been well elucidated. This study aimed to comprehensively elucidate the mutational landscape of tumor tissue samples from patients with systemic ALCL.

Methods: Thirty-six patients with systemic ALCL were enrolled in this retrospective study. Immunohistochemistry (IHC) was performed on tumor tissues at baseline to identify anaplastic lymphoma kinase () fusions. Capture-based targeted next-generation sequencing (NGS) with a panel spanning 112 lymphoma-related genes, including rearrangements, was also performed on tumor tissue samples.

Results: A total of 102 mutations were identified in the entire cohort. Among the 36 patients included in this analysis, 14 (38.8%) were positive, as determined by IHC, while NGS showed 12 patients (33.3%) to harbor rearrangements. Younger patients were more likely to have -positive ALCL (P=0.011). Patients with wild-type (WT) were more likely to have single-nucleotide variants (SNVs) and insertions or deletions (INDELs) than patients with rearrangements (P=0.027). Among the 22 patients with WT , the most commonly mutated genes were (n=6, 27.3%), followed by (n=5, 22.7%), (n=3, 13.6%), (n=3, 13.6%), (n=3, 13.6%), and (n=2, 9.1%). Mutations in , a commonly mutated gene in -negative patients, were not detected in our -negative cohort. Start-loss of beta-2-microglobulin () was detected in another patient; this patient had a favorable prognosis, with an overall survival exceeding 19 months.

Conclusions: Our study revealed the unique genomic profiles of Chinese ALCL patients and represents an incremental step in deepening the understanding of the genetic heterogeneity of ALCL patients.