Neuroblastoma is remarkable for its clinical heterogeneity and is characterized by genomic alterations that are strongly correlated with tumor behavior. The specific genes that influence neuroblastoma biology and are targeted by genomic alterations remain largely unknown. We quantified mRNA expression in a highly annotated series of 101 prospectively collected diagnostic neuroblastoma primary tumors using an oligonucleotide-based microarray. Genomic copy number status at the prognostically relevant loci 1p36, 2p24 (MYCN), 11q23, and 17q23 was determined by PCR and was aberrant in 26, 20, 40, and 38 cases, respectively. In addition, 72 diagnostic neuroblastoma primary tumors assayed in a different laboratory were used as an independent validation set. Unsupervised hierarchical clustering showed that gene expression was highly correlated with genomic alterations and clinical markers of tumor behavior. The vast majority of samples with MYCN amplification and 1p36 loss of heterozygosity (LOH) clustered together on a terminal node of the sample dendrogram, whereas the majority of samples with 11q deletion clustered separately and both of these were largely distinct from the copy number neutral group of tumors. Genes involved in neurodevelopment were broadly overrepresented in the more benign tumors, whereas genes involved in RNA processing and cellular proliferation were highly represented in the most malignant cases. By combining transcriptomic and genomic data, we showed that LOH at 1p and 11q was associated with significantly decreased expression of 122 (61%) and 88 (27%) of the genes mapping to 1p35-36 and all of 11q, respectively, suggesting that multiple genes may be targeted by LOH events. A total of 71 of the 1p35-36 genes were also differentially expressed in the independent validation data set, providing a prioritized list of candidate neuroblastoma suppressor genes. Taken together, these data are consistent with the hypotheses that the neuroblastoma transcriptome is a sensitive marker of underlying tumor biology and that chromosomal deletion events in this cancer likely target multiple genes through alteration in mRNA dosage. Lead positional candidates for neuroblastoma suppressor genes can be inferred from these data, but the potential multiplicity of transcripts involved has significant implications for ongoing gene discovery strategies. (Cancer Res 2006; 66(12): 6050-62)

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Line shapes of the zone-center optic modes Eg and A&g in Sb have been measured at 80 K by Raman scattering. The results indicate asymmetry in the wings. The E~m ode, in particular, shows a Fano line shape which is believed to arise from the interaction between the phonon and intraband electronic Raman scattering within the penetration depth of the metal. Although the cross section for the latter process is usually small for normal metals, in antimony, because of the anisotropic multivalleyed Fermi surface and small effective mass of the carriers, it is likely to be significant.The manifestation of interaction between overlapping discrete-continuum states as Fano interference in the phonon line shape in solids has been observed experimentally by Raman scattering. For insulating crystals like BaTiO3and AlPO~, the continuum is provided by phonon bands' (one or two phonons), whereas in heavily doped semiconductors like p-type Si, ' and 315 superconductors like V3Si, ' vertical interband transitions between occupied and unoccupied states give rise to a continuum of electronic energy levels overlapping the phonon frequency.In semimetals like Bi and Sb the free carriers are generally located at Brillouin-zone edges in pockets with small effective mass at the Fermi level. ' Sb with a carrier density of -10 cm provides an interesting example in which light light scattering processes can give rise to intraband intervalley transitions spanning an energy range of qc vF -250 cm, where qc is related to the inverse penetration depth of light in the medium and vF is average electron velocity at the Fermi level. In this paper we report Raman studies in Sb. Careful measurements show asymmetric line profiles for the zone-center optic phonons which we attribute to Fano-type interaction between one-phonon scattering and intraband electronic Raman scattering. Antimony has a rhombohedral crystal structure (D3$) with two atoms per unit cell. The zone-center optic phonons are Raman active but infrared inactive and can be classified into one nondegenerate mode A l and a doubly degenerate mode Eg. The corresponding Raman tensors have the following form' (hexagonal axis system is chosen here;trigonal axis is taken as the z axis):(2) (f 15 cm) lenses. An incidence angle 8 of approximately 30' was used for convenience, since for 8~30' the specularly reflected beam clears the collection lens. The light scattered in the [001] direction (with a spread of about 24' cone) was collected by a F/1 lens system and focused on the entrance slit of a homemade grating double monochromator. A polaroid was placed in the scattered beam to select diagonal (A~, + Eg ) and off-diagonal (Eg ) components of the Raman scattering tensor. Low-temperature measurements were performed using a homemade liquidnitrogen cryostat. The signal was detected using a cooled FW-130 multiplier phototube. The data were recorded in the digital mode with a spectral band pass of 2.8 cm '. Our values of phonon frequency and width are in general agreement with the earlier measurements. ...

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