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Molecular profiling of Chinese R-CHOP treated DLBCL patients: Identifying a high-risk subgroup
- Source :
- International journal of cancerREFERENCES. 147(9)
- Publication Year :
- 2019
-
Abstract
- Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naive patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.
- Subjects :
- Male
Cancer Research
DNA Mutational Analysis
Disease
Kaplan-Meier Estimate
Gastroenterology
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Child
Aged, 80 and over
Hazard ratio
Middle Aged
Oncology
Proto-Oncogene Proteins c-bcl-2
Vincristine
030220 oncology & carcinogenesis
Disease Progression
Female
Lymphoma, Large B-Cell, Diffuse
Rituximab
Adult
medicine.medical_specialty
China
Adolescent
DNA Copy Number Variations
Somatic hypermutation
03 medical and health sciences
Young Adult
Internal medicine
medicine
Biomarkers, Tumor
Humans
Clinical significance
neoplasms
Cyclophosphamide
Survival analysis
Aged
Retrospective Studies
business.industry
Gene Amplification
CD79B
medicine.disease
Lymphoma
Doxorubicin
Drug Resistance, Neoplasm
Mutation
Myeloid Differentiation Factor 88
Prednisone
Tumor Suppressor Protein p53
business
Diffuse large B-cell lymphoma
Follow-Up Studies
Subjects
Details
- ISSN :
- 10970215
- Volume :
- 147
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- International journal of cancerREFERENCES
- Accession number :
- edsair.doi.dedup.....4416df0ce83278dd32f402c4ff93cd09