Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Abbasi, MR; Rifatbegovic, F; Brunner, C; Mann, G; Ziegler, A; Pötschger, U; Crazzolara, R; Ussowicz, M; Benesch, M; Ebetsberger-Dachs, G; Chan, GCF; Jones, N; Ladenstein, R; Ambros, IM; Ambros, PF.
Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone.
Clin Cancer Res. 2017; 23(15):4224-4232
Doi: 10.1158/1078-0432.CCR-16-2082
(- Case Report)
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Benesch Martin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones.Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients.Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrow-derived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs.Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224-32. ©2017 AACR. ©2017 American Association for Cancer Research.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Aged, 80 and over -
- Bone Marrow Cells - pathology
- Child, Preschool -
- Chromosomes, Human, Pair 19 - genetics
- Clonal Evolution - genetics
- Disease-Free Survival -
- Female -
- Gene Deletion -
- Genetic Heterogeneity -
- Humans -
- Male -
- Middle Aged -
- Neoplasm Metastasis -
- Neoplasm Recurrence, Local - genetics
- Neoplasm Recurrence, Local - pathology
- Neoplasm Staging -
- Neoplasms, Second Primary - genetics
- Neoplasms, Second Primary - pathology
- Neoplastic Cells, Circulating - pathology
- Neuroblastoma - genetics
- Neuroblastoma - pathology
- Polymorphism, Single Nucleotide - genetics
- Recurrence -
- X-linked Nuclear Protein - genetics