In-house liquid biopsy solution based on hybrid-capture next-generation sequencing (NGS) technology for the ultrasensitive detection of somatic alterations in circulating cell-free DNA from plasma. Developed in collaboration with Memorial Sloan Kettering Cancer Center (MSK), it implements a robust matched tumor-normal sequencing approach (plasma cfDNA + white blood cell DNA) to filter germline variants and mutations arising from clonal hematopoiesis (CHIP).
Detailed description
Operating principle
The decentralized MSK-ACCESS® powered with SOPHiA DDM™ solution enables laboratories to implement locally the globally recognized clinical liquid biopsy assay developed by MSK, while retaining full control over their samples, data and turnaround times.
The fundamental analytical pillar of this assay is its matched tumor-normal approach: circulating cell-free DNA (cfDNA) extracted from the patient’s plasma and normal DNA obtained from peripheral blood white blood cells (WBCs, from the buffy coat) are processed jointly and simultaneously.
The protocol integrates specific adapters with CUMIN® molecular barcodes and unique dual index (UDI) primers. Molecular tagging technology enables the generation of single-read consensus sequences to correct technical PCR errors and sequencing artefacts, allowing ultrasensitive detection with a limit of detection (LOD) of 0.5% variant allele frequency (VAF).
Following targeted hybrid-capture enrichment for 147 cancer-associated genes, the libraries are sequenced at high depth on Illumina, Complete Genomics or Element Biosciences platforms. Secondary and tertiary analyses are performed on the cloud-based SOPHiA DDM™ platform, which automates molecular quality control and variant filtering. The platform connects directly to OncoKB™—MSK’s precision oncology knowledge base—and the integrated OncoPortal™ for clinical matching with targeted therapies and clinical trials.
Complete gene list
| Category | Gene list / details |
|---|---|
| Gene lista | AKT1 (3, 6, 7, 8, 9, 10, 11, 12), ALK (5, 9, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29), APC (complete CDS), AR (complete CDS), ARAF (7, 10, 11, 12, 13, 14, 15, 16), ARID1A (complete CDS), ARID2 (8), ASXL1 (complete CDS), ATM (complete CDS), B2M (1), BAP1 (complete CDS), BCL2 (2), BCOR (10), BRAF (11, 12, 13, 14, 15, 16, 17, 18), BRCA1 (complete CDS), BRCA2 (complete CDS), CARD11 (13), CBFB (2), CBL (9), CCND1 (5), CD79B (5), CDH1 (complete CDS), CDK12 (complete CDS), CDK4 (complete CDS), CDKN2A (complete CDS), CHEK2 (complete CDS), CIC (5), CREBBP (26, 27, 30), CTCF (6), CTNNB1 (3, 7, 8), DICER1 (27), DIS3 (10), DNMT3A (complete CDS), EGFR (3, 6, 7, 15, 18, 19, 20, 21, 22, 23, 24), EIF1AX (1, 2), EP300 (26, 27), ERBB2 (3, 6, 7, 8, 12, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 27), ERBB3 (3, 6, 7, 8, 9, 18, 19, 20, 21, 22, 23, 24), ERCC2 (complete CDS), ESR1 (5, 6, 7, 8b), EZH2 (16), FBXW7 (complete CDS), FGFR1 (12, 13, 14, 15, 16, 17, 18, 19), FGFR2 (3, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18), FGFR3 (7, 9, 11, 12, 13, 14, 15, 16, 17, 18), FGFR4 (13), FLT3 (14, 20), FOXA1 (2), FOXL2 (complete CDS), FOXO1 (1), FOXP1 (14), FUBP1 (14), GATA3 (complete CDS), GNA11 (5), GNAQ (5), GNAS (6, 8, 9), H3F3A (2), HIST1H3B (complete CDS), HRAS (2, 3, 4), IDH1 (4, 5), IDH2 (4), IKZF1 (8), INPPL1 (2), JAK1 (19), JAK2 (14), KDM6A (complete CDS), KEAP1 (complete CDS), KIT (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21), KNSTRN (1), KRAS (complete CDS), MAP2K1 (2, 3, 4, 5, 6, 7, 8, 9, 10, 11), MAP2K2 (2, 3, 4, 5, 6, 7, 8, 9, 10, 11), MAPK1 (7), MAX (2, 4), MED12 (2, 26), MET (13, 14, 15, 16, 17, 18, 19, 20, 21), MLH1 (complete CDS), MSH2 (complete CDS), MSH3 (7), MSH6 (complete CDS), MTOR (29, 30, 31, 39, 40, 43, 44, 46, 47, 48, 49, 50, 53, 56, 57), MYC (2), MYCN (2), MYD88 (5), MYOD1 (1), NF1 (complete CDS), NFE2L2 (2), NOTCH1 (6, 8), NPM1 (11), NRAS (2, 3, 4), NTRK1 (13, 14, 15, 16, 17), NTRK2 (15, 16, 17, 18, 19), NTRK3 (15, 16, 17, 18, 19, 20), NUP93 (2), PAK5 (4), PALB2 (complete CDS), PDGFRA (5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21), PHF6 (5, 9), PIK3CA (2, 3, 5, 6, 8, 9, 10, 11, 12, 14, 19, 20, 21), PIK3CB (24), PIK3R1 (10, 11, 13, 14), PIK3R2 (10), PIM1 (1), PMS2 (complete CDS), POLE (1, 9, 13), POT1 (6), PPM1D (complete CDS), PPP2R1A (5, 6), PPP6C (7), PRKCI (15), PTCH1 (complete CDS), PTEN (complete CDS), PTPN11 (3, 13), RAC1 (2), RAD54L (10), RAF1 (7, 10, 11, 12, 13, 14, 15, 16, 17), RB1 (complete CDS), RET (8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19), RHOA (2, 3), RIT1 (5), ROS1 (36, 37, 38, 39, 40, 41, 42), RRAS2 (1, 3), RXRA (10), SETD2 (7), SF3B1 (14, 15, 18), SMAD3 (6), SMAD4 (complete CDS), SMARCA4 (19, 25, 26), SMARCB1 (9), SOS1 (5), SPOP (4, 5), SRSF2 (1), STAT3 (20), STK11 (complete CDS), STK19 (1), TCF7L2 (14), TET2 (complete CDS), TGFBR1 (4, 9), TGFBR2 (8), TP53 (complete CDS), TP63 (9, 14), TSC1 (complete CDS), TSC2 (complete CDS), U2AF1 (2, 6), VHL (complete CDS), XPO1 (15). |
| Fusions | ALK, BRAF, EGFR, ETV6, FGFR2, FGFR3, MET, NTRK1, RET, ROS1. |
| CNVs (copy number variations) | AKT1, ALK, APC, AR, ARAF, ARID1A, ASXL1, ATM, BAP1, BRAF, BRCA1, BRCA2, CDH1, CDK12, CDK4, CDKN2A, CHEK2, CREBBP, DNMT3A, EGFR, EP300, ERBB2, ERBB3, ERCC2, ESR1, FBXW7, FGFR1, FGFR2, FGFR3, FOXA1, FOXL2, GATA3, KDM6A, KEAP1, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MSH2, MSH6, MTOR, MYC, MYCN, NF1, NTRK1, NTRK2, NTRK3, PAK5, PALB2, PDGFRA, PIK3CA, PIK3R1, PMS2, PPM1D, PTCH1, PTEN, RAF1, RB1, RET, ROS1, SF3B1, SMAD4, SMARCA4, STK11, TET2, TP53, TSC1, TSC2, VHL. |
| Additional alterations | MET exon skipping and the TERT promoter. |
Clinical applications
Benefits
Intended users
High-technology molecular diagnostic laboratories, hospital medical oncology departments, precision medicine centers and institutions conducting translational clinical research and clinical trials that require ultrasensitive liquid biopsy testing with Memorial Sloan Kettering Cancer Center’s rigorous CHIP exclusion approach.
