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To further understand the acquisition of oncogenic mutations in genes in colorectal cancer and analyse the features and type of recurring mutations.

The researchers sequenced the whole genomes of nine colorectal cancers and paired normal tissue controls. Tumour samples were taken before treatment, and SNP arrays were used to confirm tumour purity and select samples with copy-number variations suggestive of a chromosomal-instability phenotype.

439 mutations were identified and validated as somatic alterations across the nine samples. An increase in mutations at CpG sites was found, consistent with previous studies. Analysis of mutations identified 24 genes including well-known cancer-related genes such as KRAS, APC and TP53.  Also, the researchers found that in some cases genomic alterations led to functional fusion genes.

This is the first study which identifies functional fusion genes in colon cancers, though they have been previously reported in lung and prostate cancer samples. The discovery of VTI1A-TCF7L2 fusions was particularly interesting. The TCF7L2 gene encodes a transcription factor (TCF4) that controls genes essential for cell growth and specialisation. TCF7L2 is widely expressed in colorectal cancer, and its expression is inversely associated with survival.

This paper provides an excellent example of the potential of the whole-genome sequencing in our further understanding of the mechanisms of cancer formation. The discovery of a broad range of genomic alterations made possible by advanced sequencing technology has allowed the identification of important genomic rearrangements and fusion events occurring in colorectal cancer.