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Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma
- Source :
- Plos One, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, instname, PLoS ONE, Vol 14, Iss 2, p e0212813 (2019), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- PUBLIC LIBRARY SCIENCE, 2019.
-
Abstract
- Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation.
- Subjects :
- Male
B Cells
Cell Lines
Biopsy
Follicular lymphoma
medicine.disease_cause
Hematologic Cancers and Related Disorders
White Blood Cells
Animal Cells
Medicine and Health Sciences
Copy-number variation
Frameshift Mutation
Lymphoma, Follicular
B-Lymphocytes
Mutation
Multidisciplinary
Massive parallel sequencing
Cell Differentiation
Hematology
Genomics
Diffuse large B-cell lymphoma
Middle Aged
Copy Number Variation
Neoplasm Proteins
Cell Transformation, Neoplastic
Oncology
Medicine
Lymphomas
Female
Biological Cultures
Lymphoma, Large B-Cell, Diffuse
Cellular Types
Raji Cells
Research Article
Adult
Follicular Lymphoma
Immune Cells
Science
Immunology
Surgical and Invasive Medical Procedures
Biology
Research and Analysis Methods
Genome Complexity
Genetics
medicine
Humans
Antibody-Producing Cells
Aged
Blood Cells
Biology and Life Sciences
Cancers and Neoplasms
Computational Biology
Cell Biology
medicine.disease
GNA13
Lymphoma
Transformation (genetics)
Cancer research
Follow-Up Studies
Subjects
Details
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- Plos One, r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe, instname, PLoS ONE, Vol 14, Iss 2, p e0212813 (2019), PLoS ONE
- Accession number :
- edsair.doi.dedup.....25a225e2a971a2ed79224fe2519e223d