TDNA 500 copies/mL of a second PIK3CA mutation detectable in their baseline ctDNA samp sample,

TDNA 500 copies/mL of a second PIK3CA mutation detectable in their baseline ctDNA samp sample, although in lesser quantities than the the tumour mutation (FigureInterestingly, though in lesser quantities than tumour mutation (Figure 2). 2). Interestingly, all all six individuals with PIK3CA-wildtype archival tumour had detectable circulating PIK3CA individuals with PIK3CA-wildtype archival tumour had detectable circulating PIK3CA m mutations in their in their baseline plasma ctDNA. In all participants,PLK3 Accession number of copies of of PIK3 tations baseline plasma ctDNA. In all participants, the the number of copies PIK3CA mutations in ctDNA fluctuated over the the coursetreatment, with no clear trend mutations in ctDNA fluctuated over course of of therapy, with no clear trend in re in relation to remedy response or duration. A larger peakpeak quantity of mutant PIK3CA alle tion to therapy response or duration. A larger quantity of mutant PIK3CA alleles in ctDNA did not necessarily seem to correlate with with a shorter survival (Figure two). in ctDNA did not necessarily appear to correlate a shorter survival (Figure 2).3.4. Serial Tumour Biopsy three.four. 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 enough tumour material for wholefor complete exome sequencing (WES) in conjunction with archival tumo from initial from initial diagnosis. diagnosis. In both individuals, 20 with the 20 of gene mutations mutations detected, In each sufferers, fewer than fewer than somatic the somatic genedetected, such as includ predicted PARP2 medchemexpress functional (deleterious) and non-functional were widespread to all predicted functional (deleterious) and non-functional mutations, mutations, have been widespread to 3 timepoints Most mutations mutations were distinctive to one particular or all but not all th 3 timepoints (Figure S1).(Figure S1). Mostwere exclusive to a single or two but nottwothree timepoints in both individuals reflecting substantial temporal genomic heterogeneity. timepoints in both patients reflecting important temporal genomic heterogeneity. In 1 patient one patient (patient X), two tumour biopsies had been obtained at pre as well as the pre a In (patient X), two tumour biopsies had been obtained at every of your every of post copanlisib plus trastuzumab time points. In the pre-trialthe pre-trial biopsies, 80/98 (81.six ) post copanlisib plus trastuzumab time points. In biopsies, 80/98 (81.six ) somatic mutations had been shared when shared even though only of somatic gene mutations gene commatic mutations had been only 10/33 (30.three ) 10/33 (30.three ) of somatic had been mutations w mon towards the typical to the two tumour biopsies possibly reflecting far more intra-tumoural intratwo tumour biopsies taken post-trial, taken post-trial, possibly reflecting more heterogeneity as the tumour evolves. tumour evolves. moural heterogeneity as theCancers 2021, 13, 1225 Cancers 2021, 13, x9 of 13 ten ofFigure 2. (a) Serial circulating PIK3CA mutant alleles (ctDNA) in individuals with PIK3CA mutation archival tumour (n = = Figure 2. (a) Serial circulating PIK3CA mutant alleles (ctDNA) in patients with PIK3CA mutation inin archival tumour (n6); (b)(b) Serial Circulating PIK3CA mutant alleles (ctDNA) in sufferers withno PIK3CA mutation in archival tumour (n = six); six); Serial Circulating PIK3CA mutant alleles (ctDNA) in individuals with no PIK3.