TDNA 500 copies/mL of a second PIK3CA mutation detectable in their baseline ctDNA samp sample, despite the fact that in lesser quantities than the the Phospholipase A custom synthesis tumour mutation (FigureInterestingly, despite the fact that in lesser quantities than tumour mutation (Figure two). two). Interestingly, all all six sufferers with PIK3CA-wildtype archival tumour had detectable circulating PIK3CA patients with PIK3CA-wildtype archival tumour had detectable circulating PIK3CA m mutations in their in their baseline plasma ctDNA. In all participants,quantity of copies of of PIK3 tations baseline plasma ctDNA. In all participants, the the amount of copies PIK3CA mutations in ctDNA fluctuated more than the the coursetreatment, with no clear trend mutations in ctDNA fluctuated over course of of remedy, with no clear trend in re in relation to therapy response or duration. A larger peakpeak quantity of RGS8 web mutant PIK3CA alle tion to treatment response or duration. A greater quantity of mutant PIK3CA alleles in ctDNA didn’t necessarily seem to correlate with having a shorter survival (Figure 2). in ctDNA did not necessarily appear to correlate a shorter survival (Figure 2).3.4. Serial Tumour Biopsy 3.4. Serial Tumour Biopsy Sequencing Sequencing Two participants had tumour biopsies biopsies post-clinical trial with Two participants had voluntary voluntary tumour pre- and pre- and post-clinical trial with s ficient tumour material exome sequencing (WES) as well as archival tumour sufficient tumour material for wholefor whole exome sequencing (WES) together with archival tumo from initial from initial diagnosis. diagnosis. In both individuals, 20 from the 20 of gene mutations mutations detected, In each patients, fewer than fewer than somatic the somatic genedetected, like includ predicted functional (deleterious) and non-functional had been typical to all predicted functional (deleterious) and non-functional mutations, mutations, were prevalent to three timepoints Most mutations mutations had been exclusive to one particular or all but not all th three timepoints (Figure S1).(Figure S1). Mostwere special to one or two but nottwothree timepoints in each individuals reflecting important temporal genomic heterogeneity. timepoints in each individuals reflecting significant temporal genomic heterogeneity. In 1 patient one patient (patient X), two tumour biopsies were obtained at pre along with the pre a In (patient X), two tumour biopsies were obtained at every from the each and every of post copanlisib plus trastuzumab time points. Within the pre-trialthe pre-trial biopsies, 80/98 (81.6 ) post copanlisib plus trastuzumab time points. In biopsies, 80/98 (81.6 ) somatic mutations have been shared when shared when only of somatic gene mutations gene commatic mutations have been only 10/33 (30.3 ) 10/33 (30.three ) of somatic have been mutations w mon for the popular towards the two tumour biopsies possibly reflecting much more intra-tumoural intratwo tumour biopsies taken post-trial, taken post-trial, possibly reflecting extra heterogeneity because the tumour evolves. tumour evolves. moural heterogeneity as theCancers 2021, 13, 1225 Cancers 2021, 13, x9 of 13 ten ofFigure two. (a) Serial circulating PIK3CA mutant alleles (ctDNA) in sufferers with PIK3CA mutation archival tumour (n = = Figure 2. (a) Serial circulating PIK3CA mutant alleles (ctDNA) in sufferers with PIK3CA mutation inin archival tumour (n6); (b)(b) Serial Circulating PIK3CA mutant alleles (ctDNA) in individuals withno PIK3CA mutation in archival tumour (n = six); six); Serial Circulating PIK3CA mutant alleles (ctDNA) in sufferers with no PIK3.
