Table 2 Key targetable variants and associated drugs and clinical trials

GBM1

PIK3R1 R562del, MET R755fs MET 11, focal gain

BKM120,

INC280

NCT01870726

NCT02386826

GBM3

PIK3CA V344G

BKM120

NCT01870726

NCT01349660

GBM4

EGFR gain, PTEN W111C, whole arm loss

Cetuximab, Everolimus

NCT01238237

NCT01870726

GBM5

PDGFRA/KIT/KDR gain

Nilotinib

NCT01140568 NCT01871311

GBM6

PIK3CA G542K, PTEN N59 fs, EGFR whole arm gain

BKM120, Everolimus, Cetuximab

NCT02142803

NCT01349660

NCT01238237

GBM7

SMO R421*, NF1 Q270*

Vismodegib, MEK162

NCT00980343

NCT01885195

GBM8*

POLE P1505S, MSH2 splice site donor c.366 + 1G > A, High mutation burden

Pembrolizumab, Nivolumab

NCT02337686

NCT02017717

GBM9

EGFR gain, KDR R1022*, PIK3R1 E443del

Cetuximab, ABT41, Bevacizumab, BKM120

NCT02573324

NCT01349660

GBM10

MGMT loss, PTEN R130*, whole arm loss NF1 E1722*

Temozolomide, Everolimus, MEK162

NCT01885195

GBM12

EGFR A289V, focal gain, PIK3R1 D560G

BKM120, Afatanib

NCT01349660 NCT01934361

GBM13

MDM2 focal gain, CDK4 focal gain, PTEN R47S

RG7112/RG7388, AMG232, Palbociclib, Everolimus

NCT01877382 NCT02143635 NCT01227434 NCT01870726

GBM14

EGFR A289V, focal gain, PIK3R1 W597G, PTEN whole arm loss and focal deletion

BKM-120, Everolimus

NCT01349660 NCT01934361 NCT01870726

GBM15

PIK3R1 T473P, EGFR whole arm gain, CDKN2A homozygous focal deletion, PTEN whole arm loss

BKM-120, Cetuximab, ABT-414, Afatanib, ABBV-221, Palbociclib, Ribociclib, Everolimus

NCT01339052 NCT02423525 NCT02573324 NCT02365662 NCT01227434 NCT02345824

GBM16

PTEN Y16*, EGFR focal gain, PDGFRA focal gain

Everolimus, Cetuximab, ABT-414, Afatanib, ABBV-221, Nilotinib, Crenolanib

NCT02423525 NCT02573324 NCT02365662 NCT02626364 NCT01140568 NCT01871311

GBM17

BRAF V600E, EGFR gain

Vemurafanib, Cobimetinib, ABT414

NCT02537600 NCT02573324 NCT02423525

GBM21

EGFR R222C, focal gain, MET P791L, focal gain, PTEN whole arm loss, CDKN2A homozygous focal deletion

Cetuximab, ABT-414, Afatanib, ABBV-221 Crizotinib, INC280, Everolimus, Palbociclib, Ribociclib

NCT02423525 NCT02573324 NCT02365662 NCT02540161 NCT02034981 NCT02386826 NCT01227434

GBM22

PTEN V119F, whole arm loss, STAG2 focal deletion, NF1283fs, focal loss, TP53 R158H

Everolimus, Olaparib, Veliparib, MEK162, Temsirolimus/Docetaxel

NCT01390571 NCT02152892

GBM23

IDH1 R132H, RPTOR A578G

AG-120, AG-881, BAY-1436032, Everolimus, INK128

NCT02073994 NCT02481154 NCT02746081 NCT01434602 NCT02142803

GBM24

PIK3CA R93W, EGFR whole arm amplification, MET focal gain, PTEN R335*, T277I, whole arm loss, CDKN2A homozygous focal deletion, PALB2 whole arm loss

BKM-120, Cetuximab, ABT-414, Afatanib, ABBV-221, Crizotinib, INC280, Everolimus, Palbociclib, Ribociclib, Olaparib, Veliparib

NCT01870726 NCT01339052 NCT02423525 NCT02573324 NCT02365662 NCT02386826 NCT01227434 NCT02345824 NCT01390571 NCT02152982

GBM25

POLA1 G1178, MSH2 splice site donor c.366 + 1G > A, TP53 R175H, G245S, PDGFRA Y375H, PDGFRA/KIT/KDR focal gain, High mutation burden

Pembrolizumab, Nivolumab, Paclitaxel, Nilotinib

NCT02337686 NCT02017717 NCT02379416 NCT01140568 NCT01871311

GBM26

PIK3CA R88Q, MDM2 focal gain, CDK4 focal gain, PTEN whole arm loss

BKM-120, RG-7112, AMG-232, Palbociclib, Ribociclib, Everolimus

NCT01249660 NCT01339052 NCT01877282 NCT01723020 NCT01390571 NCT02152982 NCT02255461

GBM27

EGFRvIII, EGFR focal gain, CDKN2A homozygous focal deletion, PTEN whole arm loss

Afatnib, Rindopepimut, CAR-T, Cetuximab, ABT-414, Afatanib, Palbociclib, Ribociclib, Everolimus

NCT01480479 NCT02423525 NCT02664363 NCT02573324 NCT02423525 NCT00703625 NCT01390571 NCT02152982

GBM28

PIK3R1 Q579fs, PIK3CA D939G, MET focal gain, PDGFRA focal gain, CDKN2A homozygous focal deletion, PTEN whole arm loss

BKM-120, Crizotinib, INC280, Nilotinib Palbociclib, Ribociclib, Everolimus

NCT01870726 NCT01339052 NCT01870726 NCT01339052 NCT02365662 NCT01140568 NCT01390571 NCT02152982

GBM29

EGFR A289V, EGFR focal gain, PTEN R130*, whole arm loss, CDKN2A homozygous focal deletion, CDK4 focal gain

Cetuximab, ABT-414, Afatanib, Everolimus, Palbociclib, Ribociclib

NCT02573324 NCT02423525 NCT0070362 NCT01390571 NCT02152982 NCT01390571 NCT02152982

GBM31

IDH1 R132H, TSC2 P1215fs, TP53 R175H, CDKN2A homozygous focal deletion

AG-120, AG-881, BAY-1436032, Everolimus, Temsirolimus, MLN0128, Temsirolimus/Docetaxel, Palbociclib, Ribociclib

NCT02073994 NCT02481154 NCT02746081 NCT002238946 NCT02142803 NCT01390571 NCT02152982

GBM32

PIK3R1 A483P, STAG2 focal deletion, PTEN M198R, whole arm loss

BKM-120, Olaparib, Veliparib, Everolimus

NCT01870726 NCT01390571 NCT02152982 NCT01434602

GBM33

PTEN Q97*, whole arm loss, CDKN2A focal loss

Everolimus, Temsirolimus, Palbociclib, Ribociclib

NCT01390571 NCT02152982

GBM34

EGFR gain, PTEN whole arm loss, TP53 C242S, V143 M, MYCN gain

Cetuximab, ABT-414, Afatanib, Everolimus, Temsirolimus, Docetaxel, CP-0610, MK-8628, GSK2820151

NCT02573324 NCT02423525 NCT00703625 NCT02698176 NCT02630251 NCT01877382

GBM35

EGFR focal gain, PIK3R1 L372dup, CDKN2A homozygous loss, PTEN whole arm loss, KIT A207V

Cetuximab, ABT-414, Afatanib, BKM-120 Palbociclib, Ribociclib, Everolimus, Imatinib, Nilotinib

NCT02573324 NCT02423525 NCT02345824 NCT01390571 NCT02152982

GBM36

NF1 c.1062 + 1 Splice Site Donor, TP53 T211I

MEK162, Temsirolimus, Docetaxel

NCT00703625