Saturday, February 2, 2013

The future of cancer genome sequencing

Three trends in cancer genome sequencing
        No doubt that genome sequencing will dominate future cancer research and clinic. A great number of papers published in high impact journals have adopted genome sequencing to resolve questions in cancer research that were once unrealistic to answer. Many oncologists hope to acquire the genome information of patients to guide their clinical administration. A few growing biotechnology companies have launched genome sequencing based products for cancer diagnostics. Media also pay much attention to genome sequencing. The essential reason of this trend is the genomic origin of cancers. Like what famous cancer geneticist Robert A. Weinberg has proposed in one of his most broadly cited papers, cancer actually originates from genome instability and relevant mutations. Another important reason for the blossom of genome sequencing is tumor heterogeneity which means there are no two tumors alike. Only by genome sequencing can we know exactly how special a tumor is and what therapy is best for it. Thus, the capacity of detecting genome information using sequencing tool has been favored by both Ph.Ds and M.Ds.
        The genome sequencing is in adolescence for basic research and in babyhood in clinic. How will it grow up? There might be three kinds of trends.
        Single cancer cell sequencing
        There are no two pieces of leaves alike. So are tumor cells. A tumor cell’s special identity can be recognized by expressed proteins, RNAs in the cell. But the fundamental way to distinguish a tumor cell is genome sequencing. Single cancer cell sequencing is thus important.
        Sequencing itself requires a certain amount of DNA that usually cannot be acquired from a single cell. Amplification of DNA extracted from a single cell is necessary to obtain enough DNA for sequencing. Latest state-of-the-art sequencing technology is viable for single cell sequencing.
        Single cell sequencing may not be suitable for clinic because analyzing a tumor instead of a single tumor cell is more appropriate for patient’s benefit. However, it is indispensible for studying fundamental questions in cancer research like cancer origin, cancer stem cell and so on.
        Dynamic sequencing
        No man ever steps in the same river twice. Tumors change their genome quickly, especially when they undergo anti-cancer drug exposure. Genome-changed tumors may not be sensitive any more to the drug that works formerly. Finding out the changed genome information is necessary before a new therapy will be applied. This implies that the genome sequencing should be performed periodically to monitor genome dynamic so that optimized therapy can be administrated. This dynamic genome sequencing will be especially important when tumors have improved drug resistance to a drug by producing new mutations. 
        Noninvasive sequencing
        Current genome sequencing requires pathology tissues. However, sometimes acquiring pathology tissues are painful and even dangerous for patients. Melanoma represents such an example. This situation calls for noninvasive test. At least under one condition noninvasive test becomes possible. It is when tumor cells shed from the primary tumor into bloodstream and circulate there. This phenomenon is christened as circulating tumor cells. By analyzing genomes obtained from circulating tumor cells, the cancer mutation signature can be captured and appropriate therapy options can be suggested. 
        These three trends are not mutual exclusive and combining these methods will enable us to better understand cancer.

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