Cancer Genome Project

The Cancer Genome Project, based at the Wellcome Trust Sanger Institute, aims to identify sequence variants/mutations critical in the development of human cancers.

The Cancer Genome Project combines knowledge of the human genome sequence with high throughput mutation detection techniques to identify somatically acquired sequence variants/mutations and hence identify genes critical in the development of human cancers. This initiative will ultimately provide the paradigm for the detection of germline mutations in non-neoplastic human genetic diseases through genome-wide mutation detection approaches.

Overview

Small intragenic mutations are commonly found in both recessive oncogenes and dominantly acting oncogenes. Therefore the search for and detection of this type of mutation will lead to identification of both classes of oncogene, including those for which no positional mapping information is available. The presence of small intragenic mutations (in particular those that are predicted to encode truncated versions of the protein) is regarded as the strongest structural evidence that a gene is a recessive oncogene. It also is often the only class of structural change found in many dominantly acting oncogenes in human cancers. This project is systematically screening coding exons and flanking splice junctions of all genes in the human genome for somatically acquired small intragenic mutations in human cancer. This study uses DNA from primary tumours and normal genomic DNA from the same individuals in addition to cancer cell lines.

Strategy

PCR primers are designed to flank the coding exons and splice junctions of genes in the human genome. The first sets of genes include protein kinases and other genes that are potential therapeutic targets. The genes are amplified by the PCR and the products sequenced. The sequences are compared with a control samples to identify novel variants in the tumour samples. When these are found the tumour is resequenced along with its matched normal DNA to ascertain if the variant is a somatic mutation. The significance of mutated genes is evaluated by screening a larger series of cancers.

Results

The results from this work are collated and stored in COSMIC. In addition, COSMIC contains somatic mutation data that has been published in the scientific literature.

External links

* [http://www.sanger.ac.uk/genetics/CGP/ Official website]
* [http://www.sciam.com/article.cfm?id=mapping-the-cancer-genome/ Francis S. Collins and Anna D. Barker. "Mapping the Cancer Genome". Scientific American, February 2007]