Table 3

Comparative molecular profile on ctDNA between ICI initiation and late progression

patientsomatic mutations at ICI initiation (%VAF)somatic mutations at ICI progression (%VAF)new LOH of specific cancer-related genes at ICI progression
#1HOXA13 (7.6)
INSR (19.5)
APAF1 (2.0)
ATM (2.0)
HOXA13 (13.1)
FOXL2 (5.2)
BAP1, CCND3, GADD45B, HLA-A, HLA-B, PIK3R3, PTEN, SMARCD1, XPC
#2BLK (4.4)
FOXL2 (7.1)
ARID3C (3.7)
MAX (10.9)
G464V BRAF (10.6)
NUP93 (4.0)
DVL1 (4.1)
PAG1 (7.7)
LRP1B (11.5)
SHTN1 (4.7)
MAML2 (3.2)
HSPB1, STK19
#3ATR (6.9)
NF1 (6.9)
G464V BRAF (7.4)
PHOX2B (8.5)
CDKN2 (4.0)
PIM1 (8.4)
HOXA13 (6.6)
TP53 (8.3)
DNMT3B (5.2) B2M, DNAJB1, GADD45B, LTB, TGFBR2
#4AR (12.0) FAT1 (3.0)FAT1 (3.5)RASA1, SH3GL1, SMARCE1, TLR8
#5HOXA13 (12.5) G469V BRAF (3.0)
KMT2D (4.9)
BLK (3.8)
MUC1 (9.0)
CLIP1 (4.9)
RET (4.2)
FOXL2 (7.9)
ZFHX3 (5.2)
HOXA13 (17.4)
CCND3, DEK, DNAJB1, LRP5, MAP2K4, MAPK3
#6CDKN2 (1.9)
FOXL2 (5.0)
HOXA13 (9.4)
G719A EGFR (4.0)*
PTEN (2.5)*
TP53 (2.0)*
DNAJB1, NFKB2, SMARCE1
#7FOXL2 (7.3)
PHOX2B (5.8)
ARID1B (6.4)
FOXL2 (3.5)
CCND3, CXCR3, FBXO31, HSPB1, PTEN, RB1, SETD6, XPC
#8ARID1A (18.5)
KEAP1 (9.0)
ATXN2 (9.1)
LRP1B (5.5)
BCL12B (5.2)
MNX1 (11.3)
BCR (25.6)
MST1 (8.8)
CPS1 (10.7)
MYBL1 (9.6)
DOT1L (11.5)
NCOA3 (4.5)
EP300 (17.2)
NUTM2B (21.7)
EPHA5 (16.6)
PAX7 (6.0)
FAF1 (10.5)
POLD1 (12.1)
FGFR3 (6.8)
RELN (13.9)
FOXL2 (5.6)
SEC31A (5.8)
GABRA6 (13.9)
TMEM127 (15.9)
INSR (7.3)
TP53 (6.8)
FOXL2 (5.3)GADD45B, NFKBIE, NOTCH4, PCD1LG2,
PTEN, SMARCD2, TNFRSF17
  • Underlined genes correspond to new somatic mutations compared with ICI initiation.

  • *Molecular pattern determined by NGS on spinal fluid.

  • ctDNA, circulating tumor DNA; ICI, immune checkpoint inhibitor; LOH, loss of heterozygosity; NGS, next-generation sequencing; VAF, variant allelic frequency.