Purpose: Gastrointestinal stromal tumors (GIST) are a distinctive group of mesenchymal neoplasms of the gastrointestinal tract. The oncogene KIT has a central role in the pathogenesis of GIST, with c-kit receptor tyrosine kinase (KIT) protein expression being the gold standard in its diagnosis. The identification of GIST patients has become crucial, because the tyrosine kinase inhibitor Imatinib is effective in the treatment of this malignancy. However, a small set of GISTs remain unrecognized, because KIT protein expression is not always evident. The aim of this study was the identification of new markers for the differential diagnosis of GIST.Experimental Design: By analyzing publicly available data from transcriptional profiling of sarcomas, we found that protein kinase C (PKC-), a novel PKC isotype involved in T-cell activation, is highly and specifically expressed in GIST. PKC-expression in GIST was confirmed by reverse transcription-PCR and Western blot. PKC-was analyzed by immunohistochemistry in a panel of 26 GIST, 12 non-GIST soft-tissue sarcomas, and 35 tumors from other histologies.Results: We found that all of the GISTs expressed PKC-, whereas this protein was undetectable in other mesenchymal or epithelial tumors, including non-GIST KITpositive tumors. PKC-immunoreactivity was also observed in interstitial cells of Cajal.Conclusions: Our results show that PKC-is easily detected by immunohistochemistry in GIST specimens and that it could be a sensitive and specific marker for the diagnosis of this malignancy.

The diagonal and nondiagonal components of the transverse magnetoresistance have been measured, over a wide magnetic field range, in modulated doped Al0.25Ga0.75N/GaN heterostructures. The diagonal component shows electron–electron interaction in the whole magnetic field range, Shubnikov–de Hass (SdH) oscillations superimposed at high magnetic field, and weak localization at very low magnetic field. The SdH oscillations are evidence of the existence of a two-dimensional electron gas (2DEG) in the heterostructure. Only one kind of carriers is present with an electron density of 1.01×1017 m−2, an effective mass of 0.23m0 and a quantum scattering time τq=0.05 ps. From the diffusive electron–electron interaction, an impurity scattering time τee=0.044 ps, a Hartree factor F=0.25 and the Drude scattering time τ0=0.26 ps, were obtained. The weak localization yields two scattering times, an elastic scattering time τe=0.023 ps independent of the temperature, and an inelastic scattering time, τi, with a temperature dependence following the 1/τi∝T ln T law expected for the impurity contribution of the electron–electron interaction in 2D. The τq/τ0 ratio gives the dominant scattering mechanism, which in our case is 0.19. The remote ionized impurities alone do not explain this obtained ratio, while the introduction of the interface roughness could explain it.

PACS 68.55.Jk, 68.55.Ln, 73.61.Ey, 81.15.Gh, 85.30

For the cancer genomics era, there is a need for clinically annotated close-to-patient cell lines suitable to investigate altered pathways and serve as high-throughput drug-screening platforms. This is particularly important for drug-resistant tumors like chondrosarcoma which has few models available. Here we established and characterized new cell lines derived from two secondary (CDS06 and CDS11) and one dedifferentiated (CDS-17) chondrosarcomas as well as another line derived from a CDS-17-generated xenograft (T-CDS17). These lines displayed cancer stem cell-related and invasive features and were able to initiate subcutaneous and/or orthotopic animal models. Different mutations in Isocitrate Dehydrogenase-1 (IDH1), Isocitrate Dehydrogenase-2 (IDH2), and Tumor Supressor P53 (TP53) and deletion of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) were detected both in cell lines and tumor samples. In addition, other mutations in TP53 and the amplification of Mouse Double Minute 2 homolog (MDM2) arose during cell culture in CDS17 cells. Whole exome sequencing analysis of CDS17, T-CDS17, and matched patient samples confirmed that cell lines kept the most relevant mutations of the tumor, uncovered new mutations and revealed structural variants that emerged during in vitro/in vivo growth. Altogether, this work expanded the panel of clinically and genetically-annotated chondrosarcoma lines amenable for in vivo studies and cancer stem cell (CSC) characterization. Moreover, it provided clues of the genetic drift of chondrosarcoma cells during the adaptation to grow conditions.