Journal
CANCERS
Volume 14, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/cancers14205152
Keywords
primary cutaneous diffuse large B-cell lymphoma; leg type; genetic stability; survival; targeted therapies; liquid biopsies; disease monitoring
Categories
Funding
- Stichting Fonds Oncologie Holland [17.09]
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In this study, the genetic evolution of primary and relapsed/refractory disease in PCDLBCL-LT patients was investigated. The researchers found that the main driver alterations were persistently present in relapsed/refractory disease and identified novel alterations in relapsed cases. MYC rearrangements and HIST1H1E mutations were significantly associated with a worse prognosis. These findings suggest the potential for targeted therapies and molecular-based disease monitoring in this patient population.
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only --55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88 /CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/ CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients.
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