I have been introduced to genotypes data and have found some interesting driver mutations that were already discovered in cancer. However, I also have found a few mutations in some new genes. For one particular gene, I have found that mutation in almost 95% (n= 80) of cancer samples and not in controls. I was told that this could be somatic mutation, but I am finding it difficult to understand why it is somatic mutation. I would really appreciate if someone can clarify this riddle to me.
If you are doing sequencing in tumours you will be identifying both germline and somatic mutations. Depending on your allele frequency cutoffs and filtering criteria before you look at the variants, you may be looking mostly at somatic variants because tumours are constantly acquiring new mutations. If you are doing matched tumour/normal sequencing then you will be filtering out the majority of germline variants and looking only at somatic mutations. Somatic mutations just means all mutations found in somatic (as opposed to germline) cells, so all mutations that an individual has acquired during their lifetime, mostly we study these in tumours but if you picked any random skin cell from a person you would likely find some somatic mutations due to DNA damage, chemical exposure, etc.
Now, the question is whether you mean that that particular gene has some mutations (but not necessarily the same mutations) in 95% of cancer samples and not controls, or you are finding the same recurrent mutation? Are you sequencing tumours or are these germline samples from people with some hereditary cancer syndrome? What sort of filtering are you doing in order to remove common variants?
a somatic mutation is simply a mutation occurring in a somatic cell. Somatic cells are all those cells (the vast majority in our bodies) that do not belong to the germinal line (the one originating gametes). Germinal mutations are especially meaningful in biology because they can be transmitted to the progeny, and they are the driving force of evolution. Unless your tumor derives from the germ line, any new mutation you observe will be a somatic one. Of course, one can be born with some alleles exposing him to the risk of cancer: the mutation originating that allele would be a germinal one, the following mutation causing the onset of cancer (and others that might follow) would all be somatic.
So, variations that are present in all cells of a person are most likely inherited, those found in a percentage of cells from the same person are likely to be somatic mutations.
Are you sure this is not a sequencing error or bioinformatics pipeline issue? Check if this mutation occurs in an homopolymeric region, or within a di/tri nucleotides stretch or next to a primer end, those are often sources of False Positives.