Different Mutational Profiles of Subcutaneous Panniculitis-like T-cell Lymphoma and Lupus Panniculitis: An Additional Case Series.
Por:
Machan S, Rodríguez M, Manso R, Borregón J, Chamizo C, Alonso-Alonso R, Rodríguez-Peralto JL, Torres Nieto MÁ, Monteagudo C, García Toro E, Cerroni L, García C, Estrach T, García Herrera A, Ferrer B, García-Patos V, Segues N, Díaz de la Pinta FJ, Afonso-Martin JL, Peñate Y, Limeres-Gonzalez MÁ, González-Núñez MÁ, González-Cruz C, García Fernández E, Cereceda L, Minguez P, de la Fuente L, Requena L, Rodríguez-Pinilla SM
Ahead of Print:
18 jul 2024
Resumen:
BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: The aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: We studied a total of 10 SPTCL and 10 LEP patients using targeted next-generation sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: The mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: The mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.
Filiaciones:
Machan S:
Department of Dermatology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
Rodríguez M:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Manso R:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Borregón J:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Chamizo C:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Alonso-Alonso R:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Rodríguez-Peralto JL:
Hospital Universitario 12 de Octubre, Madrid, Spain
Torres Nieto MÁ:
Hospital Universitario Río Hortega, Valladolid, Spain
Monteagudo C:
Hospital Clinico Universitario de Valencia, Universidad de Valencia, Valencia, Spain
García Toro E:
Hospital Universitario de Burgos, Burgos, Spain
Cerroni L:
Dermatopathology Research Unit, Department of Dermatology, Medical University of Graz, Graz, Austria
García C:
Hospital Universitario de Canarias, Tenerife, Spain
Estrach T:
Hospital Clínic de Barcelona, Barcelona, Spain
García Herrera A:
Hospital Clínic de Barcelona, Barcelona, Spain
Ferrer B:
Hospital Vall d'Hebron, Barcelona, Spain
García-Patos V:
Hospital Vall d'Hebron, Barcelona, Spain
Segues N:
Hospital Universitario Donostia, San Sebastián, Spain
Díaz de la Pinta FJ:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Afonso-Martin JL:
Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
Peñate Y:
Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
Limeres-Gonzalez MÁ:
Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
González-Núñez MÁ:
Hospital Ciudad de Coria y Hospital San Pedro de Alcántara, Cáceres, Spain
González-Cruz C:
Hospital Vall d'Hebron, Barcelona, Spain
García Fernández E:
Department of Hematology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
Cereceda L:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
Minguez P:
Department of Genetics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Bioinformatics Unit, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain
de la Fuente L:
Department of Genetics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Bioinformatics Unit, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Requena L:
Department of Dermatology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
Rodríguez-Pinilla SM:
Department of Pathology, Fundación Jiménez Díaz-IIS, Universidad Autónoma de Madrid, Madrid, Spain
CIBERONC (Centro de Investigación Biomédica en Red de Cáncer), Spain
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