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Clonal evolution in relapsed and refractory diffuse large B-cell lymphoma is characterized by high dynamics of subclones.
Melchardt, Thomas; Hufnagl, Clemens; Weinstock, David M; Kopp, Nadja; Neureiter, Daniel; Tränkenschuh, Wolfgang; Hackl, Hubert; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N; Greil, Richard; Weigert, Oliver; Egle, Alexander.
Afiliação
  • Melchardt T; Third Medical Department at The Paracelsus Medical University Salzburg, Salzburg, Austria.
  • Hufnagl C; Salzburg Cancer Research Institute (SCRI), Salzburg, Austria.
  • Weinstock DM; Cancer Cluster Salzburg (CCS), Salzburg, Austria.
  • Kopp N; Third Medical Department at The Paracelsus Medical University Salzburg, Salzburg, Austria.
  • Neureiter D; Salzburg Cancer Research Institute (SCRI), Salzburg, Austria.
  • Tränkenschuh W; Cancer Cluster Salzburg (CCS), Salzburg, Austria.
  • Hackl H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Weiss L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Rinnerthaler G; Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • Hartmann TN; Institute of Pathology, Paracelsus Medical University Salzburg, Salzburg, Austria.
  • Greil R; Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
  • Weigert O; Third Medical Department at The Paracelsus Medical University Salzburg, Salzburg, Austria.
  • Egle A; Salzburg Cancer Research Institute (SCRI), Salzburg, Austria.
Oncotarget ; 7(32): 51494-51502, 2016 08 09.
Article em En | MEDLINE | ID: mdl-27285986
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Evolução Clonal / Taxa de Mutação / Recidiva Local de Neoplasia Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Oncotarget Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Áustria

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfoma Difuso de Grandes Células B / Evolução Clonal / Taxa de Mutação / Recidiva Local de Neoplasia Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Oncotarget Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Áustria