System instability is a major contributing factor for genetic heterogeneity. For the majority of cancers, genome instability is reflected in a large frequency of mutations in the whole genome DNA sequence (not just the protein coding regions that are only 1.5% of the genome). In whole genome sequencing of different types of cancers, large numbers of mutations were found in two breast cancers (about 20,000 point mutations), 25 melanomas (9,000 to 333,000 point mutations) and a lung cancer (50,000 point mutations and 54,000 small additions and deletions). Genome instability is also referred to as an enabling characteristic for achieving endpoints of cancer evolution.
