For some pathogenic heteroplasmic mtDNA mutations, the empiric recurrence risks are low.
Two cases (#2 and #4) had different KRAS mutations in the primary and recurrent cancer; one of these (case #2) displayed an additional TP53 mutation in the recurrence that was not present in the primary.
The primary tumours were analysed for the secondary mutations of the recurrences, which had been identified previously.
These are the recurrent mutations often with multiple alleles in figure 1 B. The recurrence of the mutations in table 1, even at low abundance, suggests that these are likely to be real population components.
Previously used datasets are based on the recurrence of mutations found in the COSMIC database [ 3, 37] or manually curated sets of cancer driver mutations [ 5, 14].
Homoplasy is the recurrence of mutations on different branches of the mtDNA phylogeny in different parts of the world.
An alternative to single gene tests is to test the recurrence of mutations in groups of genes derived from known pathways [ 7, 8] or genome-scale gene interaction networks [ 9, 10].
The presence of accompanying deleterious mutations, the high degree of recurrence of the polymorphic mutations, and the occurrence of epistatic interactions generate a highly complex interference dynamics.
Case #1 shows the same KRAS and TP53 mutations between the primary tumor and the recurrence, and case #6 has the same KRAS G12R mutation in the primary and in both metachronous pancreatic ductal adenocarcinomas.
The remaining case (#5) displayed the same KRAS mutation between the primary and the recurrence, but a different morphology, being the primary a conventional pancreatic ductal adenocarcinoma and the relapse a pancreatic ductal adenocarcinoma with micropapillary features.
