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The genetics and genomics of cancer

Abstract

The past decade has seen great strides in our understanding of the genetic basis of human disease. Arguably, the most profound impact has been in the area of cancer genetics, where the explosion of genomic sequence and molecular profiling data has illustrated the complexity of human malignancies. In a tumor cell, dozens of different genes may be aberrant in structure or copy number, and hundreds or thousands of genes may be differentially expressed. A number of familial cancer genes with high-penetrance mutations have been identified, but the contribution of low-penetrance genetic variants or polymorphisms to the risk of sporadic cancer development remains unclear. Studies of the complex somatic genetic events that take place in the emerging cancer cell may aid the search for the more elusive germline variants that confer increased susceptibility. Insights into the molecular pathogenesis of cancer have provided new strategies for treatment, but a deeper understanding of this disease will require new statistical and computational approaches for analysis of the genetic and signaling networks that orchestrate individual cancer susceptibility and tumor behavior.

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Figure 1: Breast cancer susceptibility genes.

Katie Ris

Figure 2: Risk distribution for breast cancer in the population.

Katie Ris

Figure 3: Genetic instability in ovarian cancer.
Figure 4: Loss of tumor-suppressor gene function in cancer.

Katie Ris

Figure 5: Relationship between germline and somatic events involving weak tumor susceptibility genes.

Katie Ris

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Balmain, A., Gray, J. & Ponder, B. The genetics and genomics of cancer. Nat Genet 33 (Suppl 3), 238–244 (2003). https://doi.org/10.1038/ng1107

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