Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Melchardt, T; Hufnagl, C; Weinstock, DM; Kopp, N; Neureiter, D; Tränkenschuh, W; Hackl, H; Weiss, L; Rinnerthaler, G; Hartmann, TN; Greil, R; Weigert, O; Egle, A.
Clonal evolution in relapsed and refractory diffuse large B-cell lymphoma is characterized by high dynamics of subclones.
Oncotarget. 2016; 7(32): 51494-51502.
Doi: 10.18632/oncotarget.9860
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- Co-authors Med Uni Graz
- Rinnerthaler Gabriel
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- Abstract:
- Little information is available about the role of certain mutations for clonal evolution and the clinical outcome during relapse in diffuse large B-cell lymphoma (DLBCL). Therefore, we analyzed formalin-fixed-paraffin-embedded tumor samples from first diagnosis, relapsed or refractory disease from 28 patients using next-generation sequencing of the exons of 104 coding genes. Non-synonymous mutations were present in 74 of the 104 genes tested. Primary tumor samples showed a median of 8 non-synonymous mutations (range: 0-24) with the used gene set. Lower numbers of non-synonymous mutations in the primary tumor were associated with a better median OS compared with higher numbers (28 versus 15 months, p=0.031). We observed three patterns of clonal evolution during relapse of disease: large global change, subclonal selection and no or minimal change possibly suggesting preprogrammed resistance. We conclude that targeted re-sequencing is a feasible and informative approach to characterize the molecular pattern of relapse and it creates novel insights into the role of dynamics of individual genes.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult - administration & dosage
- Aged - administration & dosage
- Aged, 80 and over - administration & dosage
- Clonal Evolution - genetics
- Female - administration & dosage
- High-Throughput Nucleotide Sequencing - administration & dosage
- Humans - administration & dosage
- Lymphoma, Large B-Cell, Diffuse - genetics, pathology
- Male - administration & dosage
- Middle Aged - administration & dosage
- Mutation - administration & dosage
- Mutation Rate - administration & dosage
- Neoplasm Recurrence, Local - genetics, pathology
- Treatment Failure - administration & dosage
- Young Adult - administration & dosage
- Find related publications in this database (Keywords)
- DLBCL
- clonal evolution
- TP53
- tumor heterogeneity
- subclonal selection