Pathogenic variants of mycosis fungoides identified using next-generation sequencing

Area of Science:

• Oncology
• Genetics
• Dermatology

Background:

• Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), presents diagnostic challenges due to its similarity to benign skin conditions.
• Delayed diagnosis of MF can lead to significant therapeutic delays, necessitating improved diagnostic methods.

Purpose of the Study:

• To explore the utility of Next-Generation Sequencing (NGS) as an adjunct diagnostic tool for MF.
• To identify novel and common pathogenic variants in CTCL to enhance diagnostic accuracy.

Main Methods:

• A pilot study utilized NGS to analyze pathogenic variants in DNA from 10 MF cases with confirmed T-cell receptor clonality.
• The GatorSeq NGS Panel and Illumina NextSeq500 were employed for sequencing, with QIAGEN Clinical Insight QCI software for variant interpretation.

Main Results:

• NGS identified eight novel mutations in genes such as HLA-DRB1, AK2, ITPKB, HLA-B, TYRO3, and CHD2.
• Previously reported mutations (DNMT3A, STAT5B) and MF-associated HLA gene mutations were also detected.
• Variants implicated in apoptotic, NF-kB, JAK-STAT, and TCR signaling pathways were identified, offering insights into MF pathogenesis.

Conclusions:

• NGS shows promise in enhancing MF diagnosis by detecting pathogenic variants specific to CTCL.
• Identifying these variants can help differentiate neoplastic MF from benign inflammatory dermatoses.
• Further research may uncover new therapeutic targets for MF.