Long-read sequencing shows complex structural variants in tumor-stage mycosis fungoides

Abstract

Mycosis fungoides is the most common cutaneous T-cell lymphoma. Recurrent copy-number variations are the main unifying mutations in this disease, but to date, a comprehensive analysis of occurrence and type of structural variants responsible for these copy-number variations remains elusive. In this study, we used Oxford Nanopore Technologies long-read sequencing to elucidate the highly rearranged genomic landscape of five mycosis fungoides samples. We show the occurrence of multiple classes of simple and complex SV and analyze the extend of tumor suppressor gene deletion by complex SVs. Furthermore, leveraging long-read data, we inferred the genomic structure of a chromothripsis event. Our findings highlight the potential of long-read sequencing as a powerful tool for comprehensive genomic analysis in mycosis fungoides.