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Genetic heterogeneity between and within tumours is a major factor determining cancer progression and therapy response. Here we examined DNA sequence and DNA copy-number heterogeneity in colorectal cancer (CRC) by targeted high-depth sequencing of 100 most frequently altered genes. In 97 samples, with primary tumours and matched metastases from 27 patients, we observe inter-tumour concordance for coding mutations; in contrast, gene copy numbers are highly discordant between primary tumours and metastases as validated by fluorescent in situ hybridization. To further investigate intra-tumour heterogeneity, we dissected a single tumour into 68 spatially defined samples and sequenced them separately. We identify evenly distributed coding mutations in APC and TP5 3 in all tumour areas, yet highly variable gene copy numbers in numerous genes. 3D morpho-molecular reconstruction reveals two clusters with divergent copy number aberrations along the proximal–distal axis indicating that DNA copy number variations are a major source of tumour heterogeneity in CRC. The contribution of intra-tumour heterogeneity is increasingly associated with resistance to therapy. Here, the authors use genomic analyses to study heterogeneity in colorectal cancer and perform in-depth reconstruction of heterogeneity in one sample.

It's time to check the industry's pulse again. In a Billboard commentary almost four years ago (Dec. 19, 1999), I called for a \"grassroots people music movement\" to \"pump creativity into the marketplace.\"

The sales power of maturing baby boomers is responsible for the trend toward mainstream acceptance of adult-oriented artists. The trend reflects the wide-ranging musical tastes and sophistication of these baby boomers.

To bring back growth, the industry needs to get behind personality radio wherever it is programming new music. Satellite radio is in the same position that FM was 35 years ago. When satellite radio provides personality-based programming that can break new artists, the industry should step up to the plate with support for promotions and contests that underwrite and promote the medium. When opportunities to advertise emerge, these should be supported as well.

Music industry sales are flat because labels are failing to promote music on a local level. Independent labels are wasting their resources trying to produce national hits when they should be focusing on local acts.