“How many genes are mutated in a human tumor?” That’s the question that a team of researchers at Johns Hopkins posed, and took a comparative genomic approach. By analyzing the sequences of 20,857 transcripts from 18,191 human genes, in 11 breast and 11 colorectal cancers, Wood et al. were able to generate a topographical representation of gene mutations. The average number of mutations per tumor was approximately 80, but ranged from 39 to 193.
The mutational landsapes of cancers are shown on this map, where each gene locus is represented as a single point. The heights of the peaks ref3lect the mutation frequency of each gene across the tumors examined. A few gene “mountains” are mutated in a large proportion of tumors; most genes are mutated in <5% of tumors and are represented as "hills" in the figure.
Wood et al. proceed to summarize how many of these mutations have something in common - functions in a number of critical signaling pathways that regulate important cell activities. Signal transduction, in other words.
The problem is - how do we proceed with drug discovery against arrays of mutated genes that are so extremely variable? The prospect of coming up with a pharmaceutical array for all of these possible gene products is mind-boggling. Researchers have to wrap their minds around this problem - how can we manipulate not just protein activity, but pathway activity, in such a highly interconnected network of protein interactions. Call it network-omics, bioinformatics, or whatever else you wish, but a new field has arisen in recent years to address such questions.
- Laura D. Wood, et al. The Genomic Landscapes of Human Breast and Colorectal Cancers. Science 16 November 2007, 318(5853):1033-1164. doi: 10.1126/science.1145720
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