Malin Nilsson

Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas

Amplifications and gains involving 1q are common abnormalities in solid tumors. Recently, an amplicon originating from 1q21–23, containing the candidate oncogenes COAS1, COAS2 and COAS3 (Chromosome One Amplified Sequence) was identified. The presence, distribution and copy number level of extra COAS sequences were investigated in 48 bone and soft tissue tumor (BSTT) samples using metaphase FISH analysis. Amplification was seen in 27/48 (56%) samples. With few exceptions, all 3 genes were involved, but on average COAS2 exhibited higher copy numbers. The presence of extra COAS signals, irrespective of copy numbers, was found at similar frequencies in different histologic tumor subtypes. However, medium or high level amplification was common in lipomatous tumors but rare in other, nonlipomatous tumors (9/21 vs. 2/27 samples). The most common localization of extra COAS signals in lipomatous tumors was in supernumerary ring and giant marker chromosomes. Among nonlipomatous tumors, the distribution of extra COAS genes was more disperse, being located in various unidentified chromosomal structures, including double minutes, and only rarely in ring chromosomes. Because MDM2 is known to be amplified frequently in BSTTs, and in particular in atypical lipomatous tumors, cases with extra copies of COAS were studied also with an MDM2 probe. Twelve out of 18 lipomatous tumors had extra copies of both COAS and MDM2, and the 2 genes were found to be coamplified and interspersed exclusively in ring and giant marker chromosomes. Also 12 out of 18 nonlipomatous tumors exhibited simultaneous gain of COAS and MDM2, but colocalization in the same chromosome was less frequent. The role of the frequent coamplification of COAS, or some other yet unknown gene in the 1q21–23 region, and MDM2 remains to be elucidated.

Molecular cytogenetic mapping of recurrent chromosomal breakpoints in tenosynovial giant cell tumors.

Abstract. Tenosynovial giant cell tumor (TGCT) is the most common benign tumor of synovium and tendon sheath. Cytogenetic data indicate that 1p11–13 is the region most frequently involved in structural rearrangements. With the aim of eventually identifying the genes associated with TGCT development, we have investigated 1p11–13 breakpoints using fluorescence in situ hybridization (FISH) analysis, with a panel of yeast artificial chromosome (YAC) probes covering 1p11–21. Twenty-six tumors were analyzed by G-banding, and 24 of these showed a breakpoint in 1p11–13. The cytogenetic findings add to previous observations that, among a variety of translocations involving 1p11–13, chromosome 2 is the most common translocation partner, with a breakpoint in 2q35–37. This aberration was found in eight cases. Other recurrent translocation partners, found in two or three cases, were 5q22–31, 11q11–12, and 8q21–22. Material from 21 tumors was available for FISH analysis, which revealed that the breakpoints clustered to one region spanned by two YAC probes, 914F6 and 885F12 located in 1p13.2, in 18 cases. Bacterial artificial chromosome probes were used to map the recurrent breakpoint on chromosome 2. In four of seven cases there was a breakpoint within the sequence covered by probe 260J21, where the RDC1 gene is located, a gene reported to fuse with HMGIC in lipomas with a 2;12 translocation.

Truncation and fusion of HMGA2 in lipomas with rearrangements of 5q32→q33 and 12q14→q15

Chromosome segment 12q13→q15 recombines with many different chromosome bands in lipomas and at least ten recurrent translocations have been identified. The HMGA2 gene is often rearranged, but little is known about the molecular consequences at other breakpoints. Fusion genes between HMGA2 (12q14→q15) and LPP (3q27→q28), LHFP (13q12) and CMKOR1 (2q37) have been reported. In the present study, eight lipomas with rearrangements involving chromosome bands 12q14→q15 and 5q32→q33 were analyzed. In chromosome 5, five of the cases had a breakpoint in the 5′ part of EBF in 5q33, while three cases had breakpoints located about 200 kb 3′ of EBF. In chromosome 12, the breakpoints clustered to the region of HMGA2. Four cases had breaks within the gene and four had breaks 5′ to HMGA2 where the gene BC058822 is located. Two versions of an HMGA2/EBF fusion transcript were detected in one case; one transcript was in frame and the other out of frame. Identical EBF/BC058822 fusion transcripts, seen in two cases, one of which also had the HMGA2/EBF transcript, were out of frame and resulted in truncation of EBF. Since EBF and HMGA2 have different orientations, the findings must be explained by complex aberrations including multiple breaks. The combined data indicate that the pathogenetically significant event is fusion, truncation or transcriptional activation of HMGA2, but it can not be excluded that EBF, which has been implicated in adipogenesis, contributes to the tumor development.

Single-electron transport in InAs nanowire quantum dots formed by crystal phase engineering

We report electrical characterization of quantum dots formed by introducing pairs of thin wurtzite (WZ) segments in zinc blende (ZB) InAs nanowires. Regular Coulomb oscillations are observed over a wide gate voltage span, indicating that WZ segments create significant barriers for electron transport. We find a direct correlation of transport properties with quantum dot length and corresponding growth time of the enclosed ZB segment. The correlation is made possible by using a method to extract lengths of nanowire crystal phase segments directly from scanning electron microscopy images, and with support from transmission electron microscope images of typical nanowires. From experiments on controlled filling of nearly empty dots with electrons, up to the point where Coulomb oscillations can no longer be resolved, we estimate a lower bound for the ZB-WZ conduction-band offset of 95 meV.

Sn-Seeded GaAs Nanowires as Self-Assembled Radial p-n Junctions

The widespread use of Au as a seed particle in the fabrication of semiconductor nanowires presents a fundamental limitation to the potential incorporation of such nanostructures into electronic devices. Although several other growth techniques have been demonstrated, the use of alternative seed particle metals remains an underexplored but potentially very promising way to influence the properties of the resulting nanowires while simultaneously avoiding gold. In this Letter, we demonstrate the use of Sn as a seed particle metal for GaAs nanowires grown by metal–organic vapor phase epitaxy. We show that vertically aligned and stacking defect-free GaAs nanowires can be grown with very high yield. The resulting nanowires exhibit Esaki diode behavior, attributed to very high n-doping of the nanowire core with Sn, and simultaneous C-doping of the radial overgrowth. These results demonstrate that the use of alternative seed particle metals is a potentially important area to explore for developing nanowire materials with controlled material properties.

Conduction Band Offset and Polarization Effects in InAs Nanowire Polytype Junctions

Although zinc-blende (ZB) and wurtzite (WZ) structures differ only in the atomic stacking sequence, mixing of crystal phases can strongly affect the electronic properties, a problem particularly common to bottom up-grown nanostructures. A lack of understanding of the nature of electronic transport at crystal phase junctions thus severely limits our ability to develop functional nanowire devices. In this work we investigated electron transport in InAs nanowires with designed mixing of crystal structures, ZB/WZ/ZB, by temperature-dependent electrical measurements. The WZ inclusion gives rise to an energy barrier in the conduction band. Interpreting the experimental result in terms of thermionic emission and using a drift-diffusion model, we extracted values for the WZ/ZB band offset, 135 ± 10 meV, and interface sheet polarization charge density on the order of 10-3 C/m2. The extracted polarization charge density is 1-2 orders of magnitude smaller than previous experimental results, but in good agreement with first principle calculation of spontaneous polarization in WZ InAs. When the WZ length is reduced below 20 nm, an effective barrier lowering is observed, indicating the increasing importance of tunneling transport. Finally, we found that band-bending at ZB/WZ junctions can lead to bound electron states within an enclosed WZ segment of sufficient length, evidenced by our observation of Coulomb blockade at low temperature. These findings provide critical input for modeling and designing the electronic properties of novel functional devices, such as nanowire transistors, where crystal polytypes are commonly found.

Electron-hole interactions in coupled InAs-GaSb quantum dots based on nanowire crystal phase templates

We report growth and characterization of a coupled quantum dot structure that utilizes nanowire templates for selective epitaxy of radial heterostructures. The starting point is a zinc blende InAs nanowire with thin segments of wurtzite structure. These segments have dual roles: they act as tunnel barriers for electron transport in the InAs core, and they also locally suppress growth of a GaSb shell, resulting in coaxial InAs-GaSb quantum dots with integrated electrical probes. The parallel quantum dot structure hosts spatially separated electrons and holes that interact due to the type-II broken gap of InAs-GaSb heterojunctions. The Coulomb blockade in the electron and hole transport is studied, and periodic interactions of electrons and holes are observed and can be reproduced by modeling. Distorted Coulomb diamonds indicate voltage-induced ground-state transitions, possibly a result of changes in the spatial distribution of holes in the thin GaSb shell.

Parallel-Coupled Quantum Dots in InAs Nanowires

We use crystal-phase tuning during epitaxial growth of InAs nanowires to create quantum dots with very strong confinement. A set of gate electrodes are used to reproducibly split the quantum dots into even smaller pairs for which we can control the populations down to the last electron. The double quantum dots, which are parallel-coupled to source and drain, show clear and stable odd-even level pairing due to spin degeneracy and the strong confinement. The combination of hard-wall barriers to source and drain, shallow interdot tunnel barriers, and very high single-particle excitation energies allow an order of magnitude tuning of the strength for the first intramolecular bond. We show examples for nanowires with different facet orientations, and suggest possible mechanisms behind the reproducible double-dot formation.