Journal
ONCOTARGET
Volume 7, Issue 32, Pages 51494-51502Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9860
Keywords
DLBCL; clonal evolution; TP53; tumor heterogeneity; subclonal selection
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Funding
- Paracelsus Medical University (PMU Grant) [E-13/17/089-MEG, R-15/03/069-MEL, E-13/18/091-EGF]
- Austrian Science Fund (FWF) [W1213] Funding Source: Austrian Science Fund (FWF)
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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.
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