Researchers from Dana-Farber Cancer Institute and the Broad Institute in US said the highly "recurrent" mutations - occurring in the tumours of many people - may be the most common mutations in melanoma cells found to date.
"This new finding represents an initial foray into the 'dark matter' of the cancer genome," said Levi Garraway, senior author of the study published in Science Express.
"In addition, this represents the discovery of two of the most prevalent melanoma gene mutations," Garraway said.
Researchers said these cancer-associated mutations are the first to be discovered in the vast regions of DNA in cancer cells that do not contain genetic instructions for making proteins.
The mutations are located in non-protein-coding DNA that regulates the activity of genes.
This non-coding DNA, much of which was previously dismissed as "junk", accounts for 99 per cent of a cell's genome.
A large number of oncogenic mutations in cancer have been identified in the past several decades, but all have been found within the actual genetic blueprints for proteins.
The newly discovered mutations affect a promoter region - a stretch of DNA code that regulates the expression of a gene - adjacent to the TERT gene.
TERT contains the recipe for making telomerase reverse transcriptase, an enzyme that can make cells virtually immortal, and is often found overexpressed in cancer cells.
A promoter region of DNA controls the rate of a gene's transcription - the copying of its DNA recipe into a message used by the cell to manufacture a protein.
"We think these mutations in the promoter region are potentially one way the TERT gene can be activated," Franklin Huang, co-first author of the report along with Eran Hodis said in a statement.
To investigate the mutation's effect, the researchers hooked the mutant TERT promoter to a gene that makes luciferase - a light-emitting protein. They observed that the mutant promoter increased the production of luciferase in laboratory cell lines.
In the same way, the scientists presume, the mutant promoter in human pigmented skin cells can send the TERT gene into overdrive, potentially contributing to the development of melanoma.
In analysing whole-genome data, the investigators discovered the two somatic, or not-inherited, mutations in 17 of 19 (89 per cent) of the tumours.
Next, they sequenced a larger number of melanoma tumours and found that the two mutations were present in 71 per cent of tumours in total.
