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Publication : Cancer genome sequencing: the challenges ahead.

First Author  Heng HH Year  2007
Journal  Bioessays Volume  29
Issue  8 Pages  783-94
PubMed ID  17621658 Mgi Jnum  J:127435
Mgi Id  MGI:3763758 Doi  10.1002/bies.20610
Citation  Heng HH (2007) Cancer genome sequencing: the challenges ahead. Bioessays 29(8):783-94
abstractText  A major challenge for The Cancer Genome Atlas (TCGA) Project is solving the high level of genetic and epigenetic heterogeneity of cancer. For the majority of solid tumors, evolution patterns are stochastic and the end products are unpredictable, in contrast to the relatively predictable stepwise patterns classically described in many hematological cancers. Further, it is genome aberrations, rather than gene mutations, that are the dominant factor in generating abnormal levels of system heterogeneity in cancers. These features of cancer could significantly reduce the impact of the sequencing approach, as it is only when mutated genes are the main cause of cancer that directly sequencing them is justified. Many biological factors (genetic and epigenetic variations, metabolic processes) and environmental influences can increase the probability of cancer formation, depending on the given circumstances. The common link between these factors is the stochastic genome variations that provide the driving force behind the cancer evolutionary process within multiple levels of a biological system. This analysis suggests that cancer is a disease of probability and the most-challenging issue to the TCGA project, as well as the development of general strategies for fighting cancer, lie at the conceptual level.
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