Genetherapy

Story Summary: These are the two main cancers in the developed world for which we know the primary exposure, explains Professor Mike Stratton, from the Cancer Genome Project at the Wellcome Trust Sanger Institute. We can also see the desperate attempts of our genome to defend itself against the damage wreaked by the chemicals in cigarette smoke or the damage from ultraviolet radiation. Our cells fight back furiously to repair the damage, but frequently lose that fight. However, with both samples, because we have produced essentially complete catalogues, we can see other, more mysterious processes acting on the DNA. Tracking them down will be our major challenge for the next few years. Identifying the causative mutations among the large number found poses a challenge, but the complete genome sequences mean, that for the first time, that challenge can be met. Nearly ten years on, we are still reaping the benefit from the first human genome sequence and we have much still to do to get to grips with these new disrupted landscapes of cancer genomes, explains Dr Peter Campbell from the Wellcome Trust Sanger Institute. We want to drive healthcare through better understanding of the biology of disease, says Sir Mark Walport, Director of the Wellcome Trust. Previous outcomes from our Cancer Genome Project are already being fed into clinical trials, and these remarkable new studies further emphasise the extraordinary scientific insights and benefits for patients that accrue from studying the genome of cancer cells. The findings from today will feed into knowledge, methods and practice in patient care. Moreover, there are more than one hundred different types of cancer and sequencing genomes is expensive. To ensure that thousands of cancers ultimately are sequenced in the same way as these two, the International Cancer Genome Consortium has been established, on the model of the Human Genome project itself to coordinate cancer genome sequencing across the globe. These catalogues of mutations across the broad diversity of cancer types will provide powerful insights into the biology of cancer and will be the foundation for understanding cancer causation and improving prevention, detection and treatment. The cancer genome is ravaged by mutations, many of which are repaired as the genome tries to defend itself. Mutations in DNA caused by, for example, cigarette smoke are passed on to every subsequent generation of daughter cells, a permanent record of the damage done. One gene – CHD7 – was found to be mutated in several SCLC samples. This work and the companion study on malignant melanoma using massively parallel sequencing portend an era in which the forces of mutagens shaping our genome can be described and the consequences of these processes can be decoded. The breadth and clarity of the view of the genome from a patient with malignant melanoma is matched only by a companion study on lung cancer, published in the same issue of Nature. But the comprehensive catalogue of mutation reveals other more unusual mutations and many not related to exposure to UV light. We have revealed the archaeology of exposure in this cancer genome, which becomes a palimpsest of successive mutations. UV-light-induced mutations leave a typical signature, forming the vast majority of the mutations. The sequence also shows the genomes attempts to protect itself from damage, with DNA repair systems most active in gene regions, whereas the regions between genes are left less well guarded. The project was led by researchers from the Wellcome Trust Sanger Institute. In 2002, this group discovered that a mutation in one gene called BRAF was important in driving development of melanoma….Read the Full Story

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