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

Abstract

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 (ALK) fusions. Capture-based targeted next-generation sequencing (NGS) with a panel spanning 112 lymphoma-related genes, including ALK 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 ALK positive, as determined by IHC, while NGS showed 12 patients (33.3%) to harbor ALK rearrangements. Younger patients were more likely to have ALK-positive ALCL (P=0.011).Patients with wild-type (WT) ALK were more likely to have single-nucleotide variants (SNVs) and insertions or deletions (INDELs) than patients with ALK rearrangements (P=0.027). Among the 22 patients with WT ALK, the most commonly mutated genes were TP53 (n=6, 27.3%), followed by NOTCH1 (n=5, 22.7%), KMT2D (n=3, 13.6%), KRAS (n=3, 13.6%), TET2 (n=3, 13.6%), and JAK1 (n=2, 9.1%). Mutations in PRDM1, a commonly mutated gene in ALK-negative patients, were not detected in our ALK-negative cohort. Start-loss of beta-2-microglobulin (B2M) 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.

JAK/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK− Anaplastic Large Cell Lymphomas

“…DNA was isolated from the FFPE samples using a QIAamp DNA FFPE tissue kit (Qiagen Inc.). DNA from 21 cases, including 14 previously reported cases,9 met the quantity and quality standards for the targeted next-generation sequencing analysis, using a custom lymphoma panel covering 112 lymphoma-related genes. The next-generation sequencing library preparation, capture-based targeted DNA sequencing, and sequencing data analysis were performed as per the methods described in a previous study 10…”

SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities

“…SWI/SNF mutations are rare (≤5-6%) in other types of T cell lymphomas, including angioimmunoblastic T cell lymphoma [ 186 – 190 ], extranodal NK/T cell lymphoma [ 159 – 163 ], monomorphic epitheliotropic intestinal T cell lymphoma [ 191 – 193 ], and anaplastic large-cell lymphoma (ALCL) [ 112 , 194 – 197 ]. The mutations, if any, mostly affect ARID1A, and many are truncating.…”