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TheraSight® Mutation Profiler for Personalized Precision Tumor Therapy

Mutanom chip technology

Gene mutations are permanent changes in individual gene segments. Such changes can either occur only in the tumor (somatic mutations, not hereditary) or in all of the body’s cells (germline mutations, hereditary). Mutations play a key part in a tumor’s genesis, its further development, and its drug sensitivity. In precision medicine, they are of vital importance. They can either be the target of new drugs or, by analyzing the changes they yield in metabolic pathways and signal cascades, indicate a specific, indirect therapeutic target. When considering the significance of mutations for tumor development and its treatment, it is necessary to differentiate between driver mutations and subordinate passenger mutations. The mutational pattern in tumor diseases varies greatly from person to person. Since more and more mutations become targets of new cancer drugs, it is imperative to know the respective tumor disease’s individual mutational status. With next-generation sequencing (NGS), a quantum leap in the technology of mutational analysis has been made. This is the basis for analyzing a large number of mutations simultaneously. The degree of parallel analysis offered by NextGen Oncology ranges from approximately 500 cancer and tumor suppressor genes (focused gene panel) to all of the human body’s more than 20.000 genes (whole exome profiling). The latter is predominantly applied in the context of the development of personalized cancer vaccines based on mutated neoantigen peptides. Depending on the clinical issue, a ~500-gene-panel might suffice. This panel covers >150 genes with recurrent hotspot mutations, >300 genes with CNV gains or loss, >200 genes with full-coding DNA sequence (CDS), >1 megabase exonic footprint for Tumor Mutational Load/Burden (TMB), and microsatellite markers for microsatellite instability/stability. 

The content of the ~500-gene Oncomine® Comprehensive Assay Plus is given in the Tables below.

Genes Assayed for the Detection of DNA Sequence Variants

ABL1, ABL2, ACVR1, AKT1, AKT2, AKT3, ALK, AR, ARAF, ATP1A1, AURKA, AURKB, AURKC, AXL, BCL2, BCL2L12, BCL6, BCR, BMP5, BRAF, BTK, CACNA1D, CARD11, CBL, CCND1, CCND2, CCND3, CCNE1, CD79B, CDK4, CDK6, CHD4, CSF1R, CTNNB1, CUL1, CYSLTR2, DDR2, DGCR8, DROSHA, E2F1, EGFR, EIF1AX, EPAS1, ERBB2, ERBB3, ERBB4, ESR1, EZH2, FAM135B, FGF7, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, FLT4, FOXA1, FOXL2, FOXO1, GATA2, GLI1, GNA11, GNAQ, GNAS, H3F3A, H3F3B, HIF1A, HIST1H1E, HIST1H2BD, HIST1H3B, HRAS, IDH1, IDH2, IKBKB, IL6ST, IL7R, IRF4, IRS4, KCNJ5, KDR, KIT, KLF4, KLF5, KNSTRN, KRAS, MAGOH, MAP2K1, MAP2K2, MAPK1, MAX, MDM4, MECOM, MED12, MEF2B, MET, MITF, MPL, MTOR, MYC, MYCN, MYD88, MYOD1, NFE2L2, NRAS, NSD2, NT5C2, NTRK1, NTRK2, NTRK3, NUP93, PAX5, PCBP1, PDGFRA, PDGFRB, PIK3C2B, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R2, PIM1, PLCG1, PPP2R1A, PPP6C, PRKACA, PTPN11, PTPRD, PXDNL, RAC1, RAF1, RARA, RET, RGS7, RHEB, RHOA, RICTOR, RIT1, ROS1, RPL10, SETBP1, SF3B1, SIX1, SIX2, SLCO1B3, SMC1A, SMO, SNCAIP, SOS1, SOX2, SPOP, SRC, SRSF2, STAT3, STAT5B, STAT6, TAF1, TERT, TGFBR1, TOP1, TOP2A, TPMT, TRRAP, TSHR, U2AF1, USP8, WAS, XPO1, ZNF217, ZNF429

Genes Assayed for the Detection of Copy Number Variations

ABCB1, ABL1, ABL2, ABRAXAS1, ACVR1B, ACVR2A, ADAMTS12, ADAMTS2, AKT1, AKT2, AKT3, ALK, AMER1, APC, AR, ARAF, ARHGAP35, ARID1A, ARID1B, ARID2, ARID5B, ASXL1, ASXL2, ATM, ATR, ATRX, AURKA, AURKC, AXIN1, AXIN2, AXL, B2M, BAP1, BARD1, BCL2, BCL2L12, BCL6, BCOR, BLM, BMPR2, BRAF, BRCA1, BRCA2, BRIP1, CARD11, CASP8, CBFB, CBL, CCND1, CCND2, CCND3, CCNE1, CD274, CD276, CDC73, CDH1, CDH10, CDK12, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CHD4, CHEK1, CHEK2, CIC, CREBBP, CSMD3, CTCF, CTLA4, CTNND2, CUL3, CUL4A, CUL4B, CYLD, CYP2C9, DAXX, DDR1, DDR2, DDX3X, DICER1, DNMT3A, DOCK3, DPYD, DSC1, DSC3, EGFR, EIF1AX, ELF3, EMSY, ENO1, EP300, EPCAM, EPHA2, ERAP1, ERAP2, ERBB2, ERBB3, ERBB4, ERCC2, ERCC4, ERRFI1, ESR1, ETV6, EZH2, FAM135B, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FAT1, FBXW7, FGF19, FGF23, FGF3, FGF4, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, FLT4, FOXA1, FUBP1, FYN, GATA2, GATA3, GLI3, GNA13, GNAS, GPS2, H3F3A, H3F3B, HDAC2, HDAC9, HLA-A, HLA-B, HNF1A, IDH2, IGF1R, IKBKB, IL7R, INPP4B, JAK1, JAK2, JAK3, KDM5C, KDM6A, KDR, KEAP1, KIT, KLF5, KMT2A, KMT2B, KMT2C, KMT2D, KRAS, LARP4B, LATS1, LATS2, MAGOH, MAP2K1, MAP2K4, MAP2K7, MAP3K1, MAP3K4, MAPK1, MAPK8, MAX, MCL1, MDM2, MDM4, MECOM, MEF2B, MEN1, MET, MGA, MITF, MLH1, MLH3, MPL, MRE11, MSH2, MSH3, MSH6, MTAP, MTOR, MUTYH, MYC, MYCL, MYCN, MYD88, NBN, NCOR1, NF1, NF2, NFE2L2, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NRAS, NTRK1, NTRK3, PALB2, PARP1, PARP2, PARP3, PARP4, PBRM1, PCBP1, PDCD1, PDCD1LG2, PDGFRA, PDGFRB, PDIA3, PGD, PHF6, PIK3C2B, PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIM1, PLCG1, PMS1, PMS2, POLD1, POLE, POT1, PPM1D, PPP2R1A, PPP2R2A, PPP6C, PRDM1, PRDM9, PRKACA, PRKAR1A, PTCH1, PTEN, PTPN11, PTPRT, PXDNL, RAC1, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, RAF1, RARA, RASA1, RASA2, RB1, RBM10, RECQL4, RET, RHEB, RICTOR, RIT1, RNASEH2A, RNASEH2B, RNF43, ROS1, RPA1, RPS6KB1, RPTOR, RUNX1, SDHA, SDHB, SDHD, SETBP1, SETD2, SF3B1, SLCO1B3, SLX4, SMAD2, SMAD4, SMARCA4, SMARCB1, SMC1A, SMO, SOX9, SPEN, SPOP, SRC, STAG2, STAT3, STAT6, STK11, SUFU, TAP1, TAP2, TBX3, TCF7L2, TERT, TET2, TGFBR2, TNFAIP3, TNFRSF14, TOP1, TP53, TP63, TPMT, TPP2, TSC1, TSC2, U2AF1, USP8, USP9X, VHL, WT1, XPO1, XRCC2, XRCC3, YAP1, YES1, ZFHX3, ZMYM3, ZNF217, ZNF429, ZRSR2

Genes Assayed for the Detection of Fusions

AKT2, ALK, AR, AXL, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, ERBB4, ERG, ESR1, ETV1, ETV4, ETV5, FGFR1, FGFR2, FGFR3, FGR, FLT3, JAK2, KRAS, MDM4, MET, MYB, MYBL1, NF1, NOTCH1, NOTCH4, NRG1, NTRK1, NTRK2, NTRK3, NUTM1, PDGFRA, PDGFRB, PIK3CA, PPARG, PRKACA, PRKACB, PTEN, RAD51B, RAF1, RB1, RELA, RET, ROS1, RSPO2, RSPO3, TERT

Genes Assayed with Full Exon Coverage

ABRAXAS1, ACVR1B, ACVR2A, ADAMTS12, ADAMTS2, AMER1, APC, ARHGAP35, ARID1A, ARID1B, ARID2, ARID5B, ASXL1, ASXL2, ATM, ATR, ATRX, AXIN1, AXIN2, B2M, BAP1, BARD1, BCOR, BLM, BMPR2, BRCA1, BRCA2, BRIP1, CALR, CASP8, CBFB, CD274, CD276, CDC73, CDH1, CDH10, CDK12, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CHEK1, CHEK2, CIC, CIITA, CREBBP, CSMD3, CTCF, CTLA4, CUL3, CUL4A, CUL4B, CYLD, CYP2C9, CYP2D6, DAXX, DDX3X, DICER1, DNMT3A, DOCK3, DPYD, DSC1, DSC3, ELF3, ENO1, EP300, EPCAM, EPHA2, ERAP1, ERAP2, ERCC2, ERCC4, ERCC5, ERRFI1, ETV6, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FAS, FAT1, FBXW7, FUBP1, GATA3, GNA13, GPS2, HDAC2, HDAC9, HLA-A, HLA-B, HNF1A, ID3, INPP4B, JAK1, JAK2, JAK3, KDM5C, KDM6A, KEAP1, KLHL13, KMT2A, KMT2B, KMT2C, KMT2D, LARP4B, LATS1, LATS2, MAP2K4, MAP2K7, MAP3K1, MAP3K4, MAPK8, MEN1, MGA, MLH1, MLH3, MRE11, MSH2, MSH3, MSH6, MTAP, MTUS2, MUTYH, NBN, NCOR1, NF1, NF2, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PALB2, PARP1, PARP2, PARP3, PARP4, PBRM1, PDCD1, PDCD1LG2, PDIA3, PGD, PHF6, PIK3R1, PMS1, PMS2, POLD1, POLE, POT1, PPM1D, PPP2R2A, PRDM1, PRDM9, PRKAR1A, PSMB10, PSMB8, PSMB9, PTCH1, PTEN, PTPRT, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L, RASA1, RASA2, RB1, RBM10, RECQL4, RNASEH2A, RNASEH2B, RNASEH2C, RNF43, RPA1, RPL22, RPL5, RUNX1, RUNX1T1, SDHA, SDHB, SDHC, SDHD, SETD2, SLX4, SMAD2, SMAD4, SMARCA4, SMARCB1, SOCS1, SOX9, SPEN, STAG2, STAT1, STK11, SUFU, TAP1, TAP2, TBX3, TCF7L2, TET2, TGFBR2, TMEM132D, TNFAIP3, TNFRSF14, TP53, TP63, TPP2, TSC1, TSC2, UGT1A1, USP9X, VHL, WT1, XRCC2, XRCC3, ZBTB20, ZFHX3, ZMYM3, ZRSR2

Most importantly, for all mutations detected a worldwide search in important renown databases is performed to identify drugs, therapies and clinical studies relevant for the specified mutation and individual disease.

NextGen Oncology offers clinical reporting of the data based on Oncomine® Knowledge Base Reporter (Thermo Fisher Scientific) and other data sources.

The Figure below shows a small excerpt of a typical Oncomine Knowledgebase Report.

Figure. Excerpt from an Oncomine® Knowledge Base Report (summary page only).

Test Requirements

Fresh or cryopreserved tumor tissues are ideal for our high-resolution chip technology. However, formalin-fixed paraffin-embedded tissues have turned out to be usually sufficient, too. Minuscule tissue samples (for instance, a few of slices from a punch biopsy or tissue collected by fine-needle aspiration biopsies) suffice. Detailed information can be found in our Specimen Collection and Transport Kits.

 

Duration of Testing

Turnaround time for our 500-gene panel is 10 working days. We will contact the respective pathological institute to arrange for the FFPE tissue blocks. A single call will do, just ring us at 0211 4477 4388 (landline) or 0171 784 989 4 (cell). We will take care of the entire logistic process for you.

We are glad to consult you in finding the right treatment!