Multi-gene NGS assay for targeted therapy selection
- Tissue-based (FFPE) sample: Actionable mutations for 12 cancers types. Drugs recommendation & drugs resistance mechanism based on FDA guidelines.
- ctDNA blood sample: Apply only for Lung (NSCLC), Breast, Colorectal, Ovarian & Gastric cancers. (Contact us for technical specification variations) (*)
(*) (Tran, Le Son, et al. 'Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients.' PLoS One 14.12 (2019): e0226193.)
High Accuracy for Reliable Results
| FFPE Sample | Sensitivity | Specificity | LOD (%VAF) |
|---|---|---|---|
| SNVs/INDELs | 94.6% | >99.0% | 1% |
| Fusions | 94.0% | >99.0% | 1% |
| Amplifications | 95.0% | 97% | — |
| Blood Sample | Sensitivity | Specificity | LOD (%VAF) |
|---|---|---|---|
| SNVs/INDELs | 91.2% | >99.0% | 0.1% |
| Fusions | >99.0% | >99.0% | 1% |
| For fusions with VAF 0.01-1%, sensitivity may decrease to -66% | |||
LOD = limit of detection; VAF = variant allele frequency
1. Tran LS, Pham HAT, Tran VU, et al. Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients. PLoS ONE. 2019;14(12):e0226193. doi:10.1371/journal.pone.0226193.
2. Hoang TPN, Nguyen TA, Tran NHB, et al. Analytical validation and clinical utilization of K-4CARETM: a comprehensive genomic profiling assay with personalized MRD detection. Frontiers in Molecular Biosciences. 2024;11. doi:10.3389/fmolb.2024.1334808
Scope of the test
01
Supplementary appendix for targeted therapy mutations
| Genes | Types of mutations | Targeted therapy | |||||||||||||||||||||||||||||||||||||
| Solid tumor cancer | |||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NTRK1, NTRK2, NTRK3 | CD74-NTRK1, MPRIP-NTRK1, PAN3-NTRK2, TRIM24-NTRK2, BTBD1-NTRK3, ETV6-NTRK3 fusion | Larotrectinib, Entrectinib | |||||||||||||||||||||||||||||||||||||
| BRAF (NM_004333.6) | V600E | Dabrafenib + Trametinib | |||||||||||||||||||||||||||||||||||||
| RET | CDCC6-RET, NCOA4-RET, KIF5B-RET, TRIM27-RET | Pralsetinib, Selpercatinib | |||||||||||||||||||||||||||||||||||||
| Lung cancer, non-small cell | |||||||||||||||||||||||||||||||||||||||
| EGFR | Exon 19 deletion or L858R | Osimertinib, Gefitinib, Erlotinib, Afatinib, Dacomitinib | |||||||||||||||||||||||||||||||||||||
| EGFR | S768I, L861Q, G719X | Afatinib, Erlotinib, Gefitinib, Dacomitinib | |||||||||||||||||||||||||||||||||||||
| EGFR | Exon 20 insertion | Mobocertinib, Amivantamab | |||||||||||||||||||||||||||||||||||||
| EGFR | T790M | Osimertinib | |||||||||||||||||||||||||||||||||||||
| ALK | ALK-EML4 fusion, ALK-HIP1 fusion, ALK-PHACTR1 fusion | Alectinib, Crizotinib, Ceritinib, Brigatinib | |||||||||||||||||||||||||||||||||||||
| ALK | G1202R | Lorlatinib | |||||||||||||||||||||||||||||||||||||
| ROS1 | CD74 | SLC34A2 | SDC4 | EZR | TPM3 | FIG1 | LRIG3 | CCD6 | KDELR2 | LRI3 | TPD52L1 fusions | Entrectinib, Crizotinib, Ceritinib | |||||||||||||||||||||||||||||||||||||
| KRAS | G12C | Sotorasib, Adagrasib | |||||||||||||||||||||||||||||||||||||
| MET | Exon 14 skipping | Capmatinib, Tepotinib, Crizotinib | |||||||||||||||||||||||||||||||||||||
| ERBB2 | Mutations, Amplification | Trastuzumab deruxtecan, Ado-Trastuzumab Emtansine | |||||||||||||||||||||||||||||||||||||
| Colorectal cancer | |||||||||||||||||||||||||||||||||||||||
| NRAS | G12[A|D|V|S|R|C], G13[A|D|V|S|R|C], Q61[K|E,P|L|R,H] | Cetuximab or panitumumab (RAS Wild Type) | |||||||||||||||||||||||||||||||||||||
| KRAS | G12[A|D|V|S|R|C], G13[A|D|V|S|R|C], Q61[K|E,P|L|R,H] | Cetuximab or panitumumab (RAS Wild Type) | |||||||||||||||||||||||||||||||||||||
| BRAF | V600E | Encorafenib + Cetuximab or Panitumumab | |||||||||||||||||||||||||||||||||||||
| ERBB2 | Amplification | Tucatinib + Trastuzumab, Lapatinib + Trastuzumab, Trastuzumab Deruxtecan | |||||||||||||||||||||||||||||||||||||
| Breast cancer | |||||||||||||||||||||||||||||||||||||||
| BRCA1, BRCA2 | Pathogenic mutation positive (germline) | Olaparib, Talazoparib | |||||||||||||||||||||||||||||||||||||
| PIK3CA | H1047[R|L|Y], E545[A|D|G|K], E542K, Q546 [EIR] | Alpelisib + Fulvestrant | |||||||||||||||||||||||||||||||||||||
| ERBB2 | Amplification | Trastuzumab, Pertuzumab, Lapatinib, Trastuzumab, Trastuzumab + Chemotherapy | |||||||||||||||||||||||||||||||||||||
| ESR1 | E380, L469V, L536, S463P, Y537, D53B | Elacestrant | |||||||||||||||||||||||||||||||||||||
| PABL2 | Pathogenic mutation positive (germline) | Olaparib | |||||||||||||||||||||||||||||||||||||
| Ovarian cancer | |||||||||||||||||||||||||||||||||||||||
| BRCA1, BRCA2 | Pathogenic mutation positive (germline or somatic) | Niraparib, Olaparib, Olaparib + Bevacizumab | |||||||||||||||||||||||||||||||||||||
| Prostate cancer | |||||||||||||||||||||||||||||||||||||||
| BRCA1, BRCA2, PALB2 | Pathogenic mutation positive (germline or somatic) | Rucaparib, Olaparib | |||||||||||||||||||||||||||||||||||||
| Pancreatic cancer | |||||||||||||||||||||||||||||||||||||||
| BRCA1, BRCA2, PALB2 | Pathogenic mutation positive (germline or somatic) | Rucaparib, Olaparib | |||||||||||||||||||||||||||||||||||||
| GIST | |||||||||||||||||||||||||||||||||||||||
| KIT | Exon [9|11|13|17] mutation | Imatinib, Sorafenib | |||||||||||||||||||||||||||||||||||||
| PDGFRA | Exon 18 mutation | Avapritinib, Dasatinib, Suntinib | |||||||||||||||||||||||||||||||||||||
| Gastric cancer | |||||||||||||||||||||||||||||||||||||||
| ERBB2 | Amplification | Trastuzumab | |||||||||||||||||||||||||||||||||||||
| Thyroid gland cancer | |||||||||||||||||||||||||||||||||||||||
| RET | M918T, M918V, R886W, A883F, A883T, G810S, G810C | Prasetinib, Selpercatinib | |||||||||||||||||||||||||||||||||||||
| Melanoma | |||||||||||||||||||||||||||||||||||||||
| BRAF | V600K | Dabrafenib + Trametinib, Encorafenib + Binimetinib | |||||||||||||||||||||||||||||||||||||
| KIT | Exon [9|11|13|17] mutation | Imatinib | |||||||||||||||||||||||||||||||||||||
| Erdheim-Chester, Langerhans cell, Rosai-Dorfman histiocytosis | |||||||||||||||||||||||||||||||||||||||
| MAP2K1 | F53L, F53_158del, Q56P, I99_K104del, L115P, R49L | Cobimetinib, Trametinib | |||||||||||||||||||||||||||||||||||||
| KRAS | G12[A|D|V|S|R|C], G13[A|D|V|S|R|C], Q61[K|E,P|L|R,H] | Cobimetinib, Trametinib | |||||||||||||||||||||||||||||||||||||
| NRAS | G12[A|D|V|S|R|C], G13[A|D|V|S|R|C], Q61[K|E,P|L|R,H] | Cobimetinib, Trametinib | |||||||||||||||||||||||||||||||||||||
| BRAF | V600K, G466K, G469V | Cobimetinib, Trametinib | |||||||||||||||||||||||||||||||||||||
| Cholagiocarcinoma | |||||||||||||||||||||||||||||||||||||||
| ERBB2 (HER2) | Amplification | Zanidatamab | |||||||||||||||||||||||||||||||||||||
| FGFR2 | FGFR2-BICC1,FGFR2-CCDC6 , other | Pemigatinib, Futibatinib | |||||||||||||||||||||||||||||||||||||
| IDH1 | R132 | Ivosidenib | |||||||||||||||||||||||||||||||||||||
| Brain Tumor | |||||||||||||||||||||||||||||||||||||||
| IDH1 | R132 | Vorasidenib | |||||||||||||||||||||||||||||||||||||
| IDH2 | R140 or R172 | Enasidenib | |||||||||||||||||||||||||||||||||||||
| Refer to NCCN 2023 and FDA | |||||||||||||||||||||||||||||||||||||||
02
Appendix of drug-resistant mutations
| Variant | Antimicrobial | Recommended timeframe | Types of cancer | Scientific evidence | |||||||||||||
| NRAS | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q61K, Q61R | Dabrafenib, Vemurafenib | On average, 6-7 months after treatment | Lung, Prostate - Rectum, Thyroid | Ufuk Degirmenci Drug resistance in targeted cancer therapies with RAF inhibitors | |||||||||||||
| Q61K, Q61R | Dabrafenib, Vemurafenib | Cancer recurrence and metastasis (RECIST 1.1) | Lung, Prostate - Rectum, Thyroid | Stephen A. Luebker* Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies | |||||||||||||
| BRAF | |||||||||||||||||
| c.139-?_1314+? del (Deletion) | Dabrafenib, Vemurafenib | On average, 6-7 months after treatment | Lung, Prostate - Rectum, Thyroid | Ufuk Degirmenci Drug resistance in targeted cancer therapies with RAF inhibitors | |||||||||||||
| c.139-?_1314+? del (Deletion) | Dabrafenib, Vemurafenib | Cancer recurrence and metastasis (RECIST 1.1) | Lung, Prostate - Rectum, Thyroid | Stephen A. Luebker* Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies | |||||||||||||
| ESR1 | |||||||||||||||||
| D538G, Y537S, Y537N, Y537C, E380Q | Endocrine Therapy | On average, 2 years after treatment | Breast | NCCN | |||||||||||||
| D538G, Y537S, Y537N, Y537C, E380Q | Endocrine Therapy | Cancer recurrence and metastasis (RECIST 1.1) | Breast | Derek Dustin 1 ESR1 mutations in breast cancer | |||||||||||||
| EGFR | |||||||||||||||||
| T790M, C797S, T745M, L718Q insertion exon 20, | Afatinib Erlotinib Gefitinib Osimertinib Tyrosine Kinase Inhibitor - NS | On average, 1 years after treatment | Lung | NCCN | |||||||||||||
| T790M, C797S, T745M, L718Q insertion exon 20, | Afatinib Erlotinib Gefitinib Osimertinib Tyrosine Kinase Inhibitor - NS | Cancer recurrence and metastasis (RECIST 1.1) | Lung | Alessandro Leonetti Resistance mechanisms to Osimertinib in EGFR-mutated non-small cell lung cancer ndro Leonetti | |||||||||||||
| ALK | |||||||||||||||||
| G1202R, G1269A, L1196M, G892A, G825R, G1202R, F1174L, I1171T, C1156Y, C1156Y | Alectinib Brigatinib Ceritinib Crizotinib Lorlatinib | On average, 1 years after treatment | Lung | NCCN | |||||||||||||
| G1202R, G1269A, L1196M, G892A, G825R, G1202R, F1174L, I1171T, C1156Y, C1156Y | Alectinib Brigatinib Ceritinib Crizotinib Lorlatinib | Cancer recurrence and metastasis (RECIST 1.1) | Lung | Yue Pan The Resistance Mechanisms and Treatment Strategies for ALK-Rearranged Non-Small Cell Lung Cancer | |||||||||||||
| K944N, p.F930S, p.V955G, p.V955I, and p.K966E, H1047RL, E545K, E542K | Trastuzumab, cetuximab, panituximab | Prior to targeted therapy treatment | Breast, Stomach, Prostate - Rectum | NCCN | |||||||||||||
| K944N, p.F930S, p.V955G, p.V955I, and p.K966E, H1047RL, E545K, E542K | Trastuzumab, cetuximab, panituximab | Cancer recurrence and metastasis (RECIST 1.1) | Breast, Stomach, Prostate - Rectum | Aryana R. Rasti PIK3CA Mutations Drive Therapeutic Resistance in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer | |||||||||||||
| HER2 (mutations) | |||||||||||||||||
| 755S, T798I, L869R | Neratinib, lapatinib | Prior to targeted therapy treatment | Breast, Stomach, Prostate - Rectum | NCCN | |||||||||||||
| 755S, T798I, L869R | Neratinib, lapatinib | Cancer recurrence and metastasis (RECIST 1.1) | Breast, Stomach, Prostate - Rectum | Ariella B. Hanker An acquired HER2 T798I gatekeeper mutation induces resistance to neratinib in a patient with HER2 mutant-driven breast cancer | |||||||||||||
| AR | |||||||||||||||||
| L702H, W742C, H875Y, T878A | Hormon therapy | Elevated PSA (Prostate-Specific Antigen) | Prostate gland | D. E. Rathkopf Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide | |||||||||||||
| L702H, W742C, H875Y, T878A | Hormon therapy | Cancer recurrence and metastasis (RECIST 1.1) | Prostate gland | Takayuki Sumiyoshi Clinical utility of androgen receptor gene aberrations in circulating cell-free DNA as a biomarker for treatment of castration-resistant prostate cancer | |||||||||||||
| MET | |||||||||||||||||
| H1094, G1163, L1195, D1228, Y1230 | Capmatinib, Tepotinib, Crizotinib | On average, 6-7 months after treatment | Lung | Gonzalo Recondo. Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14-Mutant NSCLC | |||||||||||||
| H1094, G1163, L1195, D1228, Y1230 | Capmatinib, Tepotinib, Crizotinib | Cancer recurrence and metastasis (RECIST 1.1) | Lung | Lyudmila A. Bazhenova. MET Inhibitors in NSCLC: Mechanisms of Resistance | |||||||||||||
Testing candidates
Lung
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue/blood/pleural fluid
Breast/Ovarian
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue/blood
Colorectal/Gastric
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue/blood
GIST
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue
Thyroid gland
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue
Pancreas/Prostate
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue
Solid tumor/Melanoma
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue
Erdheim-Chester, Langerhans cell, Rosai-Dorfman histiocytosis
cancer patient
Formalin fixed paraffin embedded (FFPE) tissue
Testing process
Complete the Consent Form and collect FFPE (Formalin-Fixed Paraffin-Embedded) samples or blood samples or pleural fluid samples.
Multi-gene sequence explanation (insertion-deletion mutations, gene fusion, gene amplification).
Identify mutations and drug resistance based on approvals from the U.S. Food and Drug Administration (FDA) and recommendations from the National Comprehensive Cancer Network (NCCN).
