Background
Methods
Variant Type | Genes | Technology |
---|---|---|
Single Nucleotide Variants (SNVs), Insertions, Deletions, and Indels | Hotspot: ABL1, AKT1, ALK, AR, ARAF, BRAF, BTK, CBL, CDK4, CHEK2, CSF1R, CTNNB1, DDR2, DNMT3A, EGFR, ERBB2, ERBB3, ERBB4, ESR1, EZH2, FGFR1, FGFR2, FGFR3, FLT3, FOXL2, GATA2, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, IFITM1, IFITM3, JAK1, JAK2, JAK3, KDR, KIT, KNSTRN, KRAS, MAGOH, MAP2K1, MAP2K2, MAPK1, MAX, MED12, MET, MLH1, MPL, MTOR, MYD88, NFE2L2, NPM1, NRAS, PAX5, PDGFRA, PIK3CA, PPP2R1A, PTPN11, RAC1, RAF1, RET, RHEB, RHOA, SF3B1, SMO, SPOP, SRC, STAT3, U2AF1, XPO1 | DNA-Seq |
Full Coding: APC, ATM, BAP1, BRCA1, BRCA2, CDH1, CDKN2A, FBXW7, GATA3, MSH2, NF1, NF2, NOTCH1, PIK3R1, PTCH1, PTEN, RB1, SMAD4, SMARCB1, STK11, TET2, TP53, TSC1, TSC2, VHL, WT1 | ||
Copy Number Gain | ACVRL1, AKT1, APEX1, AR, ATP11B, BCL2L1, BCL9, BIRC2, BIRC3, CCND1, CCNE1, CD274, CD44, CDK4, CDK6, CSNK2A1, DCUN1D1, EGFR, ERBB2, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, GAS6, IGF1R | |
Copy Number Loss | APC, ATM, BAP1, BRCA1, BRCA2, CDH1, CDKN2A, FBXW7, GATA3, MSH2, NF1, NF2, NOTCH1, PIK3R1, PTCH1, PTEN, RB1, SMAD4, SMARCB1, STK11, TET2, TP53, TSC1, TSC2, VHL, WT1 | |
Fusions | ABL1, AKT3, ALK, AXL, BRAF, EGFR, ERBB2, ERG, ETV1, ETV4, ETV5, FGFR1, FGFR2, FGFR3, MET, NTRK1, NTRK2, NTRK3, PDGFRA, PPARG, RAF1, RET, ROS1 | RNA-Seq |
Level 1 (Companion Diagnostics) | ||
Genomic Variant(s) | Tumor Type | Therapy(ies) |
ALK fusion | Lung | alectinib, brigatinib, ceritinib, crizotinib |
BRAF V600E or BRAF V600K mutation | Melanoma | cobimetinib + vemurafenib; dabrafenib; dabrafenib + trametinib; trametinib; vemurafenib |
BRAF V600E or BRAF V600K mutation | Lung | dabrafenib + trametinib |
BRCA mutation | Ovarian | olaparib, rucaparib |
EGFR exon 19 deletion | Lung | afatinib; bevacizumab + erlotinib; erlotinib; gefitinib; osimertinib |
EGFR exon 20 insertiona | Lung | gefitinib |
EGFR G719 mutation | Lung | afatinib; gefitinib |
EGFR L858R mutation | Lung | afatinib; bevacizumab + erlotinib; erlotinib; gefitinib; osimertinib |
EGFR L861Q mutation | Lung | afatinib; gefitinib |
EGFR S768I mutation | Lung | afatinib; gefitinib |
EGFR T790 M mutationa | Lung | gefitinib |
EGFR T790 M mutation | Lung | osimertinib |
ERBB2 amplification | Breast | ado-trastuzumab emtansine; lapatinib + aromatase inhibitor; lapatinib + chemo; lapatinib + trastuzumab; neratinib; pertuzumab + trastuzumab + chemo; trastuzumab; trastuzumab + aromatase inhibitor; trastuzumab + chemo |
ERBB2 amplification | Esophageal | trastuzumab; trastuzumab + chemo |
ERBB2 amplification | Gastric/GEJ | trastuzumab; trastuzumab + chemo |
KRAS A146 or KRAS A59 mutationa | Colorectal | cetuximab; panitumumab |
KRAS exon 2, 3 or 4 mutationa | Colorectal | cetuximab; cetuximab + chemo; panitumumab + chemo |
KRAS G12, KRAS G13, KRAS K117, or KRAS Q61 mutationa | Colorectal | cetuximab; panitumumab |
NRAS A146 or NRAS A59 mutationa | Colorectal | cetuximab; panitumumab |
NRAS exon 2, 3 or 4 mutationa | Colorectal | cetuximab; cetuximab + chemo; panitumumab + chemo |
NRAS G12, NRAS G13, NRAS K117, or NRAS Q61 mutationa | Colorectal | cetuximab; panitumumab |
ROS1 fusion | Lung | crizotinib |
Level 2 (Professional Practice Guidelines) | ||
Genomic Variant | Tumor Type | Therapy |
ALK fusion | Sarcoma | ceritinib, crizotinib |
ALK fusiona | Lung | EGFR tyrosine kinase inhibitor |
BRAF mutation | Thyroid | vemurafenib |
BRAF V600E mutation | Colorectal | cetuximab + vemurafenib + chemo; panitumumab + vemurafenib + chemo |
BRAF V600E mutation | Lung | dabrafenib; vemurafenib |
ERBB2 mutation | Lung | ado-trastuzumab emtansine |
ERBB2 mutation | Head and Neck | trastuzumab |
ERBB2 mutation | Breast | trastuzumab + chemo |
KIT exon 9 mutation | Sarcoma | imatinib |
KIT exon 11 mutation | Sarcoma | imatinib |
KIT exon 11 or KIT exon 13 mutation | Melanoma | imatinib |
KRAS mutationa | Lung | EGFR tyrosine kinase inhibitor (afatinib; erlotinib; erlotinib; gefitinib; osimertinib) |
MET amplification or MET exon 14 skipping mutation | Lung | crizotinib |
NF1 mutationa | Sarcoma | imatinib |
PDGFRA D842V mutationa | Sarcoma | dasatinib; imatinib |
RET fusion | Lung | cabozantinib; vandetanib |
RET mutation | Thyroid | vandetanib |
ROS1 fusion | Lung | alectinib; ceritinib |
ROS1 fusiona | Lung | EGFR tyrosine kinase inhibitor (afatinib; erlotinib; erlotinib; gefitinib; osimertinib) |
Results
Patients
Age | |
Median, yrs | 64 |
Range, yrs | 6–93 |
Gender, n (%) | |
Female | 359 (55%) |
Male | 298 (45%) |
Stage, n (%) | |
Stage I | 9 (1.4%) |
Stage II | 11 (1.7%) |
Stage III | 54 (8%) |
Stage IV | 506 (77%) |
Unknown | 77 (12%) |
Tumor Type, n (%) | |
Bladder | 4 (0.61%) |
Brain | 15 (2.3%) |
Breast | 34 (5%) |
Cervical | 4 (0.61%) |
Colorectal | 68 (10%) |
Endocrine | 3 (0.46%) |
Endometrial | 25 (3.8%) |
Esophageal | 13 (2%) |
Eye | 1 (0.2%) |
Female Genital | 1 (0.2%) |
Gallbladder | 3 (0.5%) |
Head and Neck | 4 (0.6%) |
Kidney and Renal Pelvis | 10 (1.5%) |
Liver and Bile Duct | 1 (0.15%) |
Lung | 205 (31%) |
Melanoma | 51 (8%) |
Mesothelioma | 4 (0.6%) |
Neuroendocrine Tumors | 14 (2.1%) |
Non-Melanoma Skin | 2 (0.3%) |
Ovarian | 44 (7%) |
Pancreatic | 9 (1.4%) |
Prostate | 34 (5%) |
Sarcoma | 87 (13%) |
Small Intestine | 3 (0.5%) |
Stomach | 3 (0.5%) |
Testicular | 1 (0.2%) |
Thymic | 3 (0.5%) |
Thyroid | 4 (0.6%) |
Unknown Primary | 7 (1%) |
Prior systemic treatment | |
Unknown | 4 (0.6%) |
0 | 156 (24%) |
1+ | 497 (76%) |
NGS test results and physician treatment recommendations by FDA evidence level
Level 1 variants
Tests with variants supported by level 1 evidence as the most actionable (n = 89) | |||
Gene | Tumor Type | Number of Detected Variants (n = 92) | Variants |
KRAS | Colorectal | 32 | Codon 12, 13, 61, 146 single nucleotide variants |
EGFR | Lung | 17 | L858R, T790 M, exon 19 deletions |
BRAF | Melanoma | 17 | V600E, V600K |
BRCA1 | Ovarian | 7 | Multiple single nucleotide variants & indels* |
BRAF | Lung | 5 | V600E |
ALK | Lung | 5 | ALK (EML4) fusion |
NRAS | Colorectal | 3 | Codon 12 & 61 single nucleotide variants |
BRCA2 | Ovarian | 3 | Multiple single nucleotide variants* |
ERBB2 | Breast | 2 | HER-2 amplification |
ROS1 | Lung | 1 | ROS1 (EZR) fusion |
Tests with variants supported by level 2 evidence as the most actionable (n = 100) | |||
Gene | Tumor Type | Number of Detected Variants (n = 109) | Detected Mutations |
KRAS | Lung | 71 | Codon 12, 13, 61, 146 single nucleotide variants & insertions |
EGFR | Lung | 9 | Atypical exon 19 indels, exon 20 insertions, G719C, S768I, L861Q |
MET | Lung | 7 | MET amplification and exon 14 skip |
NF1 | Sarcoma (GIST) | 5 | Multiple single nucleotide variants* |
KIT | Melanoma | 4 | Multiple exon 11 single nucleotide variants |
ERBB2 | Lung | 3 | E365K, Y742_A745dup |
KIT | Sarcoma (GIST) | 2 | Exon 9 and 11 single nucleotide variants |
BRAF | Colorectal | 2 | V600E |
RET | Thyroid | 1 | M918 T |
RET | Lung | 1 | RET (KIF5B) fusion |
KRAS | Colorectal | 1 | V14I |
NRAS | Colorectal | 1 | Q61R |
KIT | Sarcoma | 1 | V559D (exon 11) |
ALK | Sarcoma | 1 | ALK (TPM3) fusion |
Level 2 variants
Level 3 variants
Gene | Number of Variants | Number of Tests | % of Tests |
---|---|---|---|
TP53 | 310 | 280 | 0.43 |
ATM | 158 | 139 | 0.21 |
CDKN2A | 96 | 91 | 0.14 |
BRCA2 | 101 | 90 | 0.14 |
PTEN | 85 | 74 | 0.11 |
BRCA1 | 69 | 61 | 0.09 |
PIK3CA | 63 | 56 | 0.09 |
TSC2 | 45 | 44 | 0.07 |
KDR | 43 | 41 | 0.06 |
NF1 | 50 | 41 | 0.06 |
MET | 37 | 37 | 0.06 |
RB1 | 37 | 37 | 0.06 |
PTCH1 | 37 | 34 | 0.05 |
STK11 | 30 | 28 | 0.04 |
FBXW7 | 25 | 25 | 0.04 |
NF2 | 24 | 24 | 0.04 |
NRAS | 23 | 23 | 0.04 |
APC | 23 | 22 | 0.03 |
TSC1 | 23 | 21 | 0.03 |
KRAS | 19 | 18 | 0.03 |
IDH1 | 18 | 17 | 0.03 |
CDK4 | 18 | 17 | 0.03 |
CSF1R | 15 | 14 | 0.02 |
EGFR | 14 | 12 | 0.02 |
BRAF | 13 | 11 | 0.02 |
ERBB2 | 15 | 11 | 0.02 |
FGFR3 | 12 | 10 | 0.02 |
FGFR1 | 10 | 9 | 0.01 |
AKT1 | 8 | 8 | 0.01 |
SMO | 9 | 8 | 0.01 |
MSH2 | 9 | 6 | 0.01 |
CCND1 | 6 | 6 | 0.01 |
KIT | 7 | 6 | 0.01 |
PIK3R1 | 6 | 6 | 0.01 |
RET | 6 | 6 | 0.01 |
SMARCB1 | 5 | 4 | 0.01 |
CHEK2 | 4 | 4 | 0.01 |
CCNE1 | 4 | 4 | 0.01 |
MYC | 4 | 4 | 0.01 |
BAP1 | 4 | 4 | 0.01 |
ERBB4 | 3 | 3 | <.01 |
DDR2 | 3 | 3 | <.01 |
FLT3 | 3 | 3 | <.01 |
MAP2K1 | 3 | 3 | <.01 |
ALK | 3 | 3 | <.01 |
ESR1 | 2 | 2 | <.01 |
GNA11 | 2 | 2 | <.01 |
ERBB3 | 2 | 2 | <.01 |
HRAS | 2 | 2 | <.01 |
ABL1 | 2 | 2 | <.01 |
JAK2 | 2 | 2 | <.01 |
MTOR | 2 | 2 | <.01 |
MYCL | 2 | 2 | <.01 |
NFE2L2 | 2 | 2 | <.01 |
NTRK1 | 2 | 2 | <.01 |
MAPK1 | 2 | 2 | <.01 |
AR | 1 | 1 | <.01 |
CDK6 | 1 | 1 | <.01 |
FGFR2 | 1 | 1 | <.01 |
JAK1 | 1 | 1 | <.01 |
WT1 | 1 | 1 | <.01 |
MDM2 | 1 | 1 | <.01 |
NTRK3 | 1 | 1 | <.01 |
RAF1 | 1 | 1 | <.01 |
SRC | 1 | 1 | <.01 |
IDH2 | 1 | 1 | <.01 |