In Science this week, a team led by researchers at the University of Toronto report on the discovery that cancers with identical genomes can sometimes act differently, including how they respond to treatment. Using DNA copy number alteration profiling, sequencing, and lentiviral lineage tracking, the investigators followed the repopulation dynamics of 150 single lentiviral-marked lineages from 10 human colorectal cancers through serial xenograft passages in mice. They found that tumor cell clones from the same lineage displayed variable proliferation, persistence, and chemotherapy tolerance. The findings "reveal another layer of complexity, beyond genetic diversity, that drives intratumoral heterogeneity" of colorectal cancer.
Also in Science, investigators from the Dana-Farber Cancer Institute described a new role for the gene-silencing protein EZH2 in the progression of prostate cancer. EZH2 is a subunit of the Polycomb repressive complex 2, and it inhibits gene expression via its histone methyltransferase activity. Using cancer cell lines and tumor tissue samples, the researchers found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. "Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor," the researchers write. The findings point to the inhibition of EZH2's activation function as a potential strategy for cancer treatment.
Finally, scientists from Tufts University and Harvard Medical School present details of a new genetic screening technique that analyzes the complex protein exchanges between pathogens and their hosts. Called insertional mutagenesis and depletion, the approach combines bacterial mutagenesis and RNA interference, and the team used it to resolve a network of proteins secreted by the bacterium Legionella pneumophila to promote intracellular growth. The strategy can be used to study any interface between two organisms involving numerous interactions, the researchers say.