Table 1. Genomic alterations in the Hedgehog pathways genes detected in 19 of 186 GIST patients by the FoundationOne® assays.
Patient | Hh Pathway Gene | Alteration | Foundation Medicine Category | Allelic Frequency | Genomic Alteration | Depth of NGS Coverage | GIST Driver Gene (s) | KIT/PDGFRΑ Exon(s) | GIST Driver Gene Alteration(s) |
---|---|---|---|---|---|---|---|---|---|
1 | PTCH1 | E44G | VUS | 0.88 | missense | 478 | KIT | 11 | W557_V559>C |
1 | PTCH1 | S827G | VUS | 0.89 | missense | 714 | KIT | 11 | W557_V559>C |
2 | PTCH1 | E44G | VUS | 0.85 | missense | 506 | KIT | 11, 17 | K550_K558del, D820Y |
3 | PTCH1 | R1239Q | VUS | 0.51 | missense | 480 | SDHA | - | R171H, R451C |
3 | PTCH1 | E44del | VUS | 0.33 | inframe indel | 621 | SDHA | - | R171H, R451C |
4 | PTCH1 | V1418I | VUS | 0.51 | missense | 349 | KIT | 11, 13 | W557_K558del, V654A |
5 | PTCH1 | W1339_R1345del | likely deleterious | 0.16 | inframe indel | 535 | KIT | 11 | W557_K558del |
5 | PTCH1 | E44G | VUS | 0.51 | missense | 359 | KIT | 11 | W557_K558del |
6 | PTCH1 | PTCH1_C9orf153_truncation | likely deleterious | truncation | NF1 | - | V1146I | ||
7 | PTCH1 | S181* | likely deleterious | 0.42 | nonsense | 553 | KIT | 11 | V560D |
8 | PTCH2 | S1189T | VUS | 0.61 | missense | 345 | KIT | 11, 14 | W557_K558del, T670I |
9 | PTCH2 | A531V | VUS | 0.46 | missense | 362 | KIT | 11, 13 | W557_K558>Q, V654A |
7 | PTCH2 | P881Q | VUS | 0.11 | missense | 338 | KIT | 11 | V560D |
10 | SMO | G16_L17insL | VUS | 0.21 | inframe indel | 439 | KIT | 9 | S501_A502insAY |
11 | SMO | R671W | VUS | 0.51 | missense | 414 | KIT | 11 | V560E |
12 | SMO | R726Q | VUS | 0.89 | missense | 310 | KIT | 11, 17 | V560_E561>E, D820V, Y823D |
13 | SMO | V54M | VUS | 0.53 | missense | 131 | PDGFRΑ | 18 | D842V |
14 | SUFU | A425V | VUS | 0.05 | missense | 618 | WT | - | |
15 | SUFU | R362C | VUS | 0.5 | missense | 479 | WT | - | |
16 | GLI1 | R293C | VUS | 0.46 | missense | 428 | WT | - | |
15 | GLI1 | A745V | VUS | 0.49 | missense | 475 | WT | - | |
17 | GLI1 | splice site 913-1G>A | VUS | 0.38 | splicing | 519 | KIT | 11 | W557_K558del |
18 | GLI1 | G274C | VUS | 0.52 | missense | 923 | KIT | 11 | D579_H580insDPTQLPYD |
19 | GLI1 | P666S | VUS | 0.48 | missense | 705 | KIT | 9 | Y503_F504insAY |
19 | GLI1 | G421S | VUS | 0.48 | missense | 688 | KIT | 9 | Y503_F504insAY |
Abbreviations: NGS, next-generation sequencing; VUS, variant of unknown significance; WT, wild type tumor (lacking mutations in KIT, PDGFRA, BRAF, KRAS, HRAS, NF1, and SDH subunits).