Table 2

Summary of integrative sequencing results for each patient. Key actionable or informative mutations nominated for the four individual tumors described in this study. Patients 1 and 2 were carried out as pilot samples, whereas patients 3 and 4 were enrolled on the MI-ONCOSEQ clinical protocol. PTEN, phosphatase and tensin homolog; PI3K, phosphatidylinositol 3-kinase; AR, androgen receptor; TMPRSS2-ERG fusion, involving TMPRSS2 (transmembrane protease, serine 2) and ERG (ETS transcription factor); CPNE4-NEK11 fusion, involving copine IV and NIMA kinase family member; PARP, poly(adenosine diphosphate–ribose) polymerase; PLK1, polo-like kinase 1; CDK8, cyclin-dependent kinase 8; BRAF, v-raf murine sarcoma viral oncogene homolog B1; MEK, mitogen-activated or extracellular signal–regulated protein kinase kinase; CDKN2C, cyclin-dependent kinase inhibitor C.

No.DiagnosisAge
(years)
Previous therapiesSequence resultsPotential pathways for
therapeutic intervention
Examples of approved or
investigational agents
1Metastatic
castrate-resistant
prostate cancer
67Leuprolide + bicalutamidePTEN deletionPI3K inhibitorsBEZ235, GDC-0941, XL147
DiethylstilbestrolAR amplificationAndrogen signalingAbiraterone, MDV3100
NY-ESO vaccine studyTMPRSS2-ERG
rearrangement
PARP inhibitorsOlaparib, BSI-201, ABT-888
Azacytidine + valproic
acid study
CPNE4-NEK11
rearrangement
(NIMA kinases?)??
TP53 mutation
2Metastatic
prostate cancer
61Hormone naïve
(newly diagnosed)
PTEN deletionPI3K inhibitorsBEZ235, GDC-0941, XL147
TMPRSS2-ERG
rearrangement
PARP inhibitors
(UMich trial)
Olaparib, BSI-201, ABT-888
PLK1 outlier
expression
Polo kinase inhibitorsBI2536, GSK461364A, ON-01910
TP53 mutation
3Metastatic
colorectal cancer
46FOLFOX + cetuximabNRAS mutationBRAF and MEK inhibitorsPLX4032, GSK2118436, AZD6244
Irinotecan + cetuximab
phase 1: TAK-901
CDK8 amplificationPI3K inhibitorsBEZ235, GDC-0941, XL147
CDK inhibitorsFlavopiridol, PD0332991
4Metastatic
melanoma
48Multiple surgical
resections
HRAS mutationBRAF and MEK inhibitorsPLX4032, GSK2118436, AZD6244
CDKN2C
rearrangement
PI3K inhibitorsBEZ235, GDC-0941, XL147
CDK inhibitorsFlavopiridol, PD0332991