Proposal and validation of a method to classify genetic subtypes of diffuse large B cell lymphoma.

Autor: Pedrosa L; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain.; PhD Program in Molecular Biosciences, Doctoral School, Universidad Autónoma de Madrid, Madrid, Spain., Fernández-Miranda I; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain.; PhD Program in Molecular Biosciences, Doctoral School, Universidad Autónoma de Madrid, Madrid, Spain., Pérez-Callejo D; Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.; PhD Program in Medicine and Surgery, Doctoral School, Universidad Autónoma de Madrid, Madrid, Spain., Quero C; Medical Oncology Department, Hospital Universitario Virgen de La Victoria, Malaga, Spain., Rodríguez M; Pathology Department, Hospital Fundación Jiménez Díaz, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Martín-Acosta P; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Molecular Pathology Laboratory, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain., Gómez S; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain., González-Rincón J; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Santos A; Molecular Pathology Laboratory, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain., Tarin C; Bioinformatics Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Madrid, Spain.; Basic Medical Sciences, Faculty of Medicine, Universidad CEU San Pablo, Madrid, Spain., García JF; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Pathology Department, MD Anderson Cancer Center, Madrid, Spain., García-Arroyo FR; Medical Oncology Department, Complejo Hospitalario de Pontevedra, Pontevedra, Spain., Rueda A; Medical Oncology Department, Hospitales Universitarios Regional y Virgen de La Victoria, IBIMA, Malaga, Spain., Camacho FI; Pathology Department, Hospital Universitario de Getafe, Madrid, Spain., García-Cosío M; Pathology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Heredero A; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain., Llanos M; Medical Oncology Department, Hospital Universitario de Canarias, Tenerife, Spain., Mollejo M; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.; Pathology Department, Complejo Hospitalario de Toledo, Toledo, Spain., Piris-Villaespesa M; Haematology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Gómez-Codina J; Medical Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain., Yanguas-Casás N; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain., Sánchez A; Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain., Piris MA; Pathology Department, Hospital Fundación Jiménez Díaz, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain., Provencio M; Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain., Sánchez-Beato M; Lymphoma Research Group, Medical Oncology Department, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda, Madrid, Spain. msbeato@idiphim.org.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. msbeato@idiphim.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Jan 21; Vol. 11 (1), pp. 1886. Date of Electronic Publication: 2021 Jan 21.
DOI: 10.1038/s41598-020-80376-0
Abstrakt: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N1 2-S , EZB 2-S , MCD 2-S , BN2 2-S , and ST2 2-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST2 2-S is the group with the best clinical outcome and N1 2-S , the more aggressive one. EZB 2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.
Databáze: MEDLINE
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