Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression - Inserm - Institut national de la santé et de la recherche médicale
Article Dans Une Revue Blood Advances Année : 2024

Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression

Chip Stewart
Sahir Javed

Résumé

Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage.
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inserm-04782305 , version 1 (14-11-2024)

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Léa Fléchon, Inès Arib, Ankit K Dutta, Lama Hasan Bou Issa, Romanos Sklavenitis-Pistofidis, et al.. Genomic profiling of mycosis fungoides identifies patients at high risk of disease progression. Blood Advances, 2024, 8 (12), pp.3109 - 3119. ⟨10.1182/bloodadvances.2023012125⟩. ⟨inserm-04782305⟩
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