Advanced Bioinformatics Services

How to identify driver mutations in cancer?

Cancer driver mutations are somatic mutations within both oncogenes and tumour-supressors which medited the key roles in initiation and maintainace of a cancer. Driver mutations should not be confised with so-called passenger mutations, which occured mainly as a consequences of impariment of DNA repairing mechanisms in tumour cells. Identification of cancer driver mutations is critical for selecting an efficient anti-cancer therapy in personalized oncology. At the same time, since many driver mutations occur at low frequencies, it remains challenging to distinguish them from passenger mutations, especially in the highly heterogenous tumour samples. The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium have generated comprehensive databases of significantly mutated genes across all major cancer types.

Over the last years a number of bioinformatics approaches for determining cancer driver mutations have been suggested. Those include: 

1) Cancer-specific High-throughput Annotation of Somatic Mutations (CHASM) [PMID: 19654296]

2) Oncodrive-fm [PMID: 22904074]

3) Functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns [PMID: 21727090]

4) MutSigCV pipeline [PMID: 23770567]

5) Mutational Significance in Cancer (MuSiC) pipeline [PMID: 22759861]

6) Cancer driver annotation (CanDrA) tool [PMID: 24205039]

7) ANNOVAR [PMID: 20601685]