Mutations of p53, the vast majority within the sequence-specific DNA-binding domain of the protein, produce mutant proteins unable to bind to and transactivate the target genes that mediate tumor suppression [48] [50].
This indicates that despite the apparent high ratio of missense to silent mutations, the vast majority of mtDNA mutations are passengers with no convincing evidence suggesting the existence of driver mitochondrial DNA mutations.
Theoretically, one could have mutations where vast tracts of junk DNA that may have served a purpose in the ancient past are recruited for a new use.
As both are large multi-exon genes, mutation screening of BRCA1/ BRCA2 is technically challenging, because each gene harbors more than 1,000 different disease-associated mutations, the vast majority of which are individually rare.
A role for PRDM1 in lymphoma biology was first implicated when inactivating nonsense mutations, the vast majority of which associated with allelic deletions, were found to be present in almost a quarter of diffuse large B-cell lymphoma (DLBCL) of the non-germinal center (GC) B-cell/activated B-cell subtype.
Although next-generation sequencing enables the collection of vast amounts of data, mutations accumulate heterogeneously across the genome.
The extremely high number of HL-causing genes, as well as the low frequency of most known mutations, leave the vast majority of patients with no definitive genetic diagnosis, principally because the screening of all known deafness genes by traditional mutation analysis methods is unfeasible.
Of the known disease-causing missense mutations, the vast majority (up to 80%) resulted in protein destabilization [ 4].
Yet even this high incidence represents only a small fraction of chromosome mutations since the vast majority are lethal and result in prenatal death or stillbirth.
Activating mutations of the Kras gene are common to the vast majority of human PDA.
