Novel bioinformatic classification system for genetic signatures identification in diffuse large B-cell lymphoma

Autor: Ying Wang, Yang Cao, Mei' Lan Zhang, Xiao' Hong Tan, Yu' Qi Guan, Jian' Feng Zhou, Ken H. Young, Na Wang, Jiachen Wang, Liang Huang, Li Yang, Ke' Feng Shen, Hao' Dong Cai, Min Xiao, Wei Zhang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Cancer Research
DNA Mutational Analysis
Genes
myc
Disease
Mutually exclusive events
Signature
Translocation
Genetic
Cohort Studies
0302 clinical medicine
immune system diseases
hemic and lymphatic diseases
Sequencing
In Situ Hybridization
Fluorescence
High-Throughput Nucleotide Sequencing
Middle Aged
Classification
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Oncology
030220 oncology & carcinogenesis
Proto-Oncogene Proteins c-bcl-6
Female
Identification (biology)
Lymphoma
Large B-Cell
Diffuse
Algorithms
CD79 Antigens
Research Article
Adult
China
Prognostic factor
Computational biology
Biology
lcsh:RC254-282
03 medical and health sciences
Artificial Intelligence
Genetics
medicine
Humans
Gene
Aged
Retrospective Studies
CD79B
medicine.disease
Genes
bcl-2
Lymphoma
030104 developmental biology
DLBCL
Myeloid Differentiation Factor 88
Transcriptome
Diffuse large B-cell lymphoma
Genes
Neoplasm
Random forest
Zdroj: BMC Cancer, Vol 20, Iss 1, Pp 1-12 (2020)
BMC Cancer
ISSN: 1471-2407
Popis: Background Diffuse large B-cell lymphoma (DLBCL) is a spectrum of disease comprising more than 30% of non-Hodgkin lymphomas. Although studies have identified several molecular subgroups, the heterogeneous genetic background of DLBCL remains ambiguous. In this study we aimed to develop a novel approach and to provide a distinctive classification system to unravel its molecular features. Method A cohort of 342 patient samples diagnosed with DLBCL in our hospital were retrospectively enrolled in this study. A total of 46 genes were included in next-generation sequencing panel. Non-mutually exclusive genetic signatures for the factorization of complex genomic patterns were generated by random forest algorithm. Results A total of four non-mutually exclusive signatures were generated, including those with MYC-translocation (MYC-trans) (n = 62), with BCL2-translocation (BCL2-trans) (n = 69), with BCL6-translocation (BCL6-trans) (n = 108), and those with MYD88 and/or CD79B mutations (MC) signatures (n = 115). Comparison analysis between our model and traditional mutually exclusive Schmitz’s model demonstrated consistent classification pattern. And prognostic heterogeneity existed within EZB subgroup of de novo DLBCL patients. As for prognostic impact, MYC-trans signature was an independent unfavorable prognostic factor. Furthermore, tumors carrying three different signature markers exhibited significantly inferior prognoses compared with their counterparts with no genetic signature. Conclusion Compared with traditional mutually exclusive molecular sub-classification, non-mutually exclusive genetic fingerprint model generated from our study provided novel insight into not only the complex genetic features, but also the prognostic heterogeneity of DLBCL patients.
Databáze: OpenAIRE
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