Albert Einstein Cancer Center

Single-cell transcription site activation predicts chemotherapy response in human colorectal tumors

Candidate gene and pathway approaches, and unbiased gene expression profiling, have identified marker signatures predictive of tumor phenotypes. However, application of such information to evaluation of tumors in the clinic is limited by tumor cell heterogeneity. The Singer laboratory developed a novel FISH method that detects transcriptional activation of individual genes at their site in single cells in the interphase nucleus. This was applied to predict relative sensitivity of colorectal cancer cells to 5-FU, using FISH with probes targeted to nascent mRNAs to measure the number of individual cells with active transcription sites for a panel of candidate genes. The study revealed that the transcriptional status of four key genes, thymidylate synthase, MORF-related gene X (MRGX), Bcl2-antagonist/killer (BAK), and ATPase, Cu(2+) transporting beta polypeptide (ATP7B), accurately predicted response to 5-FU in the tumors from a small number of patients with colon cancer. This approach allows the identification of minute cell populations that may exhibit relative resistance to chemotherapy 

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