PloS one, 2014-09, Vol.9 (9), p.e106575-e106575
2014
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Details
- Autor(en) / Beteiligte
- Titel
- Platform comparison for evaluation of ALK protein immunohistochemical expression, genomic copy number and hotspot mutation status in neuroblastomas
- Ist Teil von
- PloS one, 2014-09, Vol.9 (9), p.e106575-e106575
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- ALK is an established causative oncogenic driver in neuroblastoma, and is likely to emerge as a routine biomarker in neuroblastoma diagnostics. At present, the optimal strategy for clinical diagnostic evaluation of ALK protein, genomic and hotspot mutation status is not well-studied. We evaluated ALK immunohistochemical (IHC) protein expression using three different antibodies (ALK1, 5A4 and D5F3 clones), ALK genomic status using single-color chromogenic in situ hybridization (CISH), and ALK hotspot mutation status using conventional Sanger sequencing and a next-generation sequencing platform (Ion Torrent Personal Genome Machine (IT-PGM)), in archival formalin-fixed, paraffin-embedded neuroblastoma samples. We found a significant difference in IHC results using the three different antibodies, with the highest percentage of positive cases seen on D5F3 immunohistochemistry. Correlation with ALK genomic and hotspot mutational status revealed that the majority of D5F3 ALK-positive cases did not possess either ALK genomic amplification or hotspot mutations. Comparison of sequencing platforms showed a perfect correlation between conventional Sanger and IT-PGM sequencing. Our findings suggest that D5F3 immunohistochemistry, single-color CISH and IT-PGM sequencing are suitable assays for evaluation of ALK status in future neuroblastoma clinical trials.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0106575Titel-ID: cdi_plos_journals_1560109229
- Format
- –
- Schlagworte
- ALK protein, Animals, Antibodies, Biology and Life Sciences, Biomarkers, Cell adhesion & migration, Child, Child, Preschool, Children & youth, Clinical trials, Color, Copy number, Correlation, Diagnostic systems, DNA sequencing, Evaluation, Female, Formaldehyde, Gene amplification, Gene expression, Gene sequencing, Genomes, Genomics, Hot spots, Humans, Hybridization, Immunoglobulins, Immunohistochemistry, In Situ Hybridization, Infant, Infant, Newborn, Kinases, Laboratories, Lung cancer, Lymphoma, Lymphomas, Medical research, Medicine, Medicine and Health Sciences, Mice, Mice, Inbred BALB C, Mutation, Mutation hot spots, Neuroblastoma, Neuroblastoma - genetics, Neuroblastoma - metabolism, Paraffin, Pathology, Protein expression, Proteins, Receptor Protein-Tyrosine Kinases - genetics, Receptor Protein-Tyrosine Kinases - metabolism, Women