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- Schleiermacher, G., et al.
(author)
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Emergence of New ALK Mutations at Relapse of Neuroblastoma
- 2014
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:25, s. 2727-2734
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Journal article (peer-reviewed)abstract
- Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000 x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.
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| 3. |
- Shekhter, Robert I., 1947, et al.
(author)
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Mechanically controlled spin-selective transport
- 2014
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121. ; 90:4
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Journal article (peer-reviewed)abstract
- A device enabling mechanically controlled spin and electric transport in mesoscopic structures is proposed. It is based on the transfer of electrons through weak links formed by suspended nanowires, on which the charge carriers experience a strong Rashba spin-orbit interaction that twists their spins. It is demonstrated that when the weak link bridges two magnetically polarized electrodes, a significant spintro-voltaic effect takes place. Then, by monitoring the generated voltage, one is able to measure electronic spins accumulated in the electrodes, induced, e.g., by circularly polarized light or, alternatively, the amount of spin twisting. Mechanically tuning the device by bending the nanowire allows one to achieve full control over the spin orientations of the charge carriers.
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