Table 2.

Selected mutations showing clonal evolution between diagnostic (T1) and relapse (T2) tumors

SampleGeneChrPositionT1 VAFT2 VAFMethod (T1)Method (T2)EffectAA change
MT-260FOXO113412397360.000.09AmpliconAmpliconMissenseS205N
MT-260MLL212494226050.000.26AmpliconExomeSplice site
MT-260TNFRSF14124881660.000.29AmpliconExomeFrameshift deletion
MT-198MYD883381826410.090.20CaptureCaptureMissenseL273P
MT-439SOCS116113491340.000.22CaptureCaptureFrameshift deletion
QC2-04STAT612574966610.010.35AmpliconAmpliconMissenseD419G
QC2-07FOXO113412402800.010.45AmpliconCaptureMissenseT24A
QC2-07GNAI23502895460.000.93AmpliconAmpliconMissenseG45W
QC2-07TP531775775630.000.77AmpliconExomeMissenseS240G
QC2-20MLL2a12494259500.300.41AmpliconExomeNonsenseQ4180b
QC2-20CD79B17620066600.000.36CaptureCaptureFrameshift deletion
QC2-20CCND36419036880.000.35CaptureCaptureMissenseI290R
QC2-20RB113489541980.010.77AmpliconAmpliconNonsenseR467b
QC2-25CD79B17620067990.000.94AmpliconAmpliconMissenseY197D
QC2-25NFKBIE6442327380.080.85AmpliconCaptureFrameshift deletion
QC2-32EZH2b71485087270.250.32AmpliconAmpliconMissenseY646S
QC2-34EZH2b71485087280.140.25CaptureCaptureMissenseY646N
QC2-34BCL2c18609857270.000.38CaptureCaptureMissenseH58L
QC2-34MEF2Bc19192600450.000.47CaptureCaptureMissenseD83V
QC2-34ARID1A1271059300.000.43AmpliconAmpliconFrameshift insertion
QC2-34MLL371520123670.000.48AmpliconAmpliconMissenseD149V
QC2-34CSPP18679766920.000.39AmpliconAmpliconMissenseE20G
QC2-34TBL1XR131767679010.000.67AmpliconExomeMissenseW196R
QC2-34STAT612574966620.000.43AmpliconAmpliconMissenseD419N
QC2-35TNFRSF14b124898180.160.11CaptureCaptureMissenseG72D
QC2-35CARD11b729838870.110.11CaptureCaptureFrameshift Deletion
QC2-35STAT6b12574966620.170.12CaptureCaptureMissenseD419H
QC2-35NFKBIZ31015724310.000.04AmpliconExomeMissenseA354D
QC2-39B2M15450037460.230.80AmpliconCaptureMissenseM2R
QC2-39FOXO113412400150.090.40AmpliconCaptureMissenseG335A
QC2-39NFKBIEb6442294830.080.23AmpliconCaptureFrameshift insertion
QC2-39SOCS116113490040.000.45AmpliconCaptureMissenseC332Y
  • NOTE: Suspected driver mutations identified in each tumor (T2) sample were selected for sequencing in T1 to assess their presence and clonal abundance at the time of diagnosis. Patients for which at least one mutation showed clear evidence for clonal evolution relative to other variants in the tumor are included. VAF changes likely resulting from variability in tumor cellularity between the samples are not shown.

  • Abbreviations: Chr, chromosome; T1, tumor at diagnosis; T2, tumor at relapse; VAF, variant allele fraction; AA, amino acid change where “– “ predicts for a truncated protein.

  • aAdjustment of VAFs for tumor purity estimates affects whether these mutations underwent clonal expansion (see Supplementary Fig. S4). After adjustment, the VAF for the EZH2 mutation in QC2-32 clearly increased at relapse, whereas the NFKBIE mutations in QC2-39 appear stable following correction for tumor purity.

  • bVAF change was not reproduced by a targeted capture-based sequencing of this sample (Supplementary Table S6).

  • cAdditional mutations in this gene with similar VAF changes were detected in this sample and a representative is shown here.