In addition to the simulated hotspots on chromosomes 5, 7, and 15, Figure 1A shows a few spurious hotspots, including a big hotspot on chromosome 8.
Except for the hotspot in the same region on c19 for VW and FW resistance, other hotspots including 8 hotspots for RKN resistance did not overlap with any of the resistance QTL hotspots for VW and FW.
Other "hotspots" include Australia, Hawaii, South Africa, and California.
This region includes "mutation hotspots" located between exons 5 and 8 that have a higher percentage of mutations, comprising approximately 30% of all known mutations [ 27, 28].
The TP53 protein has three major functional domains: a transactivation domain at its N-terminal, a central DNA-binding domain (which includes mutation hotspots) and tetramerization and regulatory domains at the C-terminal.
Sixty-six mutation positions were identified, including five mutation hotspots: U25A, C26A, G54A, U193C and U281A.
The primer sets used in these reactions are listed in Table S1 in Additional file 1. Exons that had sequence homology with a known PIK3CA pseudogene were not sequenced; however, the sequenced exons included all common mutation hotspots.
The final two domains in the gene, the PI3Ka helical domain and the PI3_PI4_kinase domain, contain known somatic missense mutation hotspots in a variety of cancer types including colon and breast cancer [ 31].
Primers were designed to amplify PIK3CA fragments that span the exon 9 hotspot mutation region including the p.E542X and p.E545X mutations, and the exon 20 region including the hotspot mutations p.H1047X, p.H1048X and p.G1049X (Additional file 1: Table S1).
The accumulated mutations differ across mutator strains, displaying base-substitution biases, allele-specific mutation hotspots, and break-associated mutation clustering.
