Somatic Tumor Panel for treatment decision support

Information

The CeGaT Somatic Tumor Panel comprises 710 genes with known mutations that can have an impact on tumor development. In addition to sequencing exonic regions of these 710 genes we analyze selected translocations in 29 genes. For the detection of somatic mutations a normal tissue sample (usually blood) is needed in addition to a sample of the tumor. The identification of somatic mutations provides a more detailed diagnosis of tumors and can support treatment decision.

Method

Enrichment, sequencing and validation
To ensure a sufficient tumor content (at least 20%) in the DNA sample macro dissection might be necessary. The enrichment of the coding regions and the adjacent intronic regions is performed using a hybridization in-Solution technology. High-throughput sequencing is performed using the Illumina HiSeq platform (paired-end, minimum of 2×100 bp, mean coverage of 500–1,000).

Computational analysis
Reads are mapped to the reference genome (hg19), variants are detected (SNPs, SNVs, small deletions and insertions), and the variants are annotated with from Ensembl, dbSNP and Exome Variant Server. Variants found in the tumor are compared to the normal tissue for the identification of somatic mutations.

Results

A medical report is issued by our team of experienced scientists and geneticists. Somatic mutations found in the 710 genes are listed in a table. The list comprises pathogenic and unclear variants. Regions with insufficient coverage will be specified.

Required material

For the analysis we require both tumor and normal tissue.

Tumor material:

  • DNA (> 200 ng) or
  • FFPE tumor block or
  • Tissue slides (minimum 10 slides).
  • If possible: H&E-stained slides with tumor area distinctly labeled. Please report the tumor content (of the labeled tumor area).

Normal tissue:

  • 3-5 ml EDTA blood or
  • 2 µg DNA or
  • FFPE block with normal tissue of the patient.
Notes

Please note

  • Next-generation high-throughput sequencing is a cost-efficient screening method to test for pathogenic mutations in disease associated genes. We cannot rule out that additional mutations could have been found by conventional sequencing methods, or the unlikely possibility that mutations were not detected in regions solely analyzed by next-generation high-throughput sequencing.
  • To ensure the quality of our findings, we require a coverage of at least 30 reads per base. Insufficiently covered regions are listed in the report.
  • The investigation of large deletions and duplications is not reliably possible by next-generation high-throughput sequencing.
  • Mutations in unanalyzed regions of the genes mentioned below (e.g. underrepresented coding regions, introns, promoter and enhancer regions) cannot be excluded.
  • Due to the rapid increase in scientific data the interpretation of the pathogenicity of variants may be different in the future.
  • As required by German law, according to German Gendiagnostikgesetz GenDG), a genetic counseling and a written consent of the patient (contained in the CeGaT order form) is required. Patients should be informed of the results of the genetic analysis in the context of a genetic counseling. For questions feel free to contact us.

Somatic cancer - treatment decision panel (710 genes, TUM01)

ABL1, ABL2, ACD, AIP, AJUBA, AKT1, AKT2, AKT3, ALK, AMER1, ANKRD26, APC, AR, ARAF, ARHGAP35, ARID1A, ARID1B, ARID2, ARID5B, ASXL1, ASXL2, ATG2B, ATM, ATP1A1, ATR, ATRX, AURKA, AURKB, AURKC, AXIN1, AXIN2, AXL, B2M, BAP1, BARD1, BCL10, BCL11A, BCL11B, BCL2, BCL3, BCL6, BCL9, BCOR, BCORL1, BCR, BIRC2, BIRC3, BIRC5, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD3, BRD4, BRIP1, BTK, BTNL2, BUB1B, C11ORF30, CALR, CAMK2G, CARD11, CASP8, CBFB, CBL, CBLB, CBLC, CCDC6, CCND1, CCND2, CCND3, CCNE1, CD274, CD38, CD52, CD58, CD79A, CD79B, CD82, CDC73, CDH1, CDH11, CDH2, CDK12, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CEBPA, CEP57, CHD1, CHD2, CHD4, CHEK1, CHEK2, CIC, CIITA, CKS1B, CNOT3, COL1A1, COMMD1, CREB1, CREBBP, CRKL, CRTC1, CRTC2, CSF1R, CSF2, CSF3R, CSMD1, CSNK1A1, CTCF, CTLA4, CTNNA1, CTNNB1, CUL4B, CUX1, CXCR4, CYLD, CYP2A7, DAXX, DCC, DDB2, DDR1, DDR2, DDX11, DDX3X, DDX41, DEK, DHFR, DICER1, DIS3, DIS3L2, DKC1, DNMT1, DNMT3A, DOT1L, DPYD, EBP, EGFR, EGLN1, EGR2, EGR3, ELAC2, ELANE, ELF3, EML4, EP300, EPAS1, EPCAM, EPHA2, EPHA3, EPHA4, EPHB4, EPHB6, ERBB2, ERBB3, ERBB4, ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERG, ERRFI1, ESR1, ESR2, ETNK1, ETS1, ETV1, ETV4, ETV5, ETV6, EWSR1, EXO1, EXT1, EXT2, EZH1, EZH2, FAM175A, FAM46C, FAN1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, FAS, FAT1, FBXW7, FES, FGF10, FGF14, FGF19, FGF2, FGF23, FGF3, FGF4, FGF5, FGF6, FGFBP1, FGFR1, FGFR2, FGFR3, FGFR4, FH, FKBP1A, FLCN, FLI1, FLT1, FLT4, FOXA1, FOXA2, FOXE1, FOXL2, FOXO1, FOXO3, FOXP1, FOXQ1, FRK, FRS2, FUBP1, FUS, FYN, G6PD, GABRA6, GALNT12, GATA1, GATA2, GATA3, GATA4, GATA6, GLDN, GLI1, GLI2, GNA11, GNA13, GNAQ, GNAS, GPC3, GPER1, GPR124, GREM1, GRIN2A, GRM3, GSK3A, H3F3A, HCK, HGF, HIF1A, HIST1H3B, HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLF, HMGA2, HMGN1, HMOX2, HNF1A, HNF1B, HOXB13, HOXD8, HRAS, HSD3B1, HSP90AA1, HSP90AB1, ID3, IDH1, IDH2, IFNGR1, IFNGR2, IGF1R, IGF2, IGF2R, IKBKB, IKBKE, IKZF1, IKZF3, IL1B, IL1RN, IL2, IL21R, IL6, IL6ST, IL7R, ING4, INPP4B, INPPL1, IRF1, IRS2, ITK, JAK1, JAK2, JAK3, JUN, KAT6A, KDM5A, KDM5C, KDM6A, KDR, KEAP1, KIAA1549, KIT, KLF2, KLF4, KLHDC8B, KLHL6, KMT2A, KMT2B, KMT2C, KMT2D, KRAS, LATS1, LATS2, LCK, LIG4, LIMK2, LMO1, LRP1B, LRRK2, LTK, LYN, LZTR1, MAD2L2, MAFB, MAGEA1, MAGI1, MAGI2, MAML1, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7, MAP3K1, MAP3K14, MAP3K3, MAP3K4, MAP3K6, MAPK1, MAPK11, MAPK12, MAPK3, MAPK8IP1, MAX, MBD1, MC1R, MCL1, MDC1, MDM2, MDM4, MECOM, MED12, MEF2B, MEN1, MET, MGA, MGMT, MITF, MLH1, MLH3, MLLT10, MLLT3, MN1, MPL, MRE11A, MS4A1, MSH2, MSH3, MSH4, MSH5, MSH6, MSR1, MST1R, MTHFR, MTOR, MTRR, MUC1, MUC16, MUTYH, MXI1, MYB, MYC, MYCL, MYCN, MYD88, MYH11, MYH9, NBN, NCOA1, NCOA3, NCOR1, NF1, NF2, NFE2L2, NFKB1, NFKB2, NFKBIA, NFKBIE, NIN, NLRC5, NOP10, NOTCH1, NOTCH2, NOTCH3, NOTCH4, NPM1, NQO1, NR1I3, NRAS, NRG2, NSD1, NT5C2, NTHL1, NTRK1, NTRK2, NTRK3, NUMA1, NUP98, PAK3, PALB2, PALLD, PARK2, PARP1, PARP2, PARP4, PAX3, PAX5, PAX7, PBK, PBRM1, PBX1, PDCD1, PDCD1LG2, PDF, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB, PDK1, PGR, PHF6, PHOX2B, PIAS4, PIGA, PIK3C2A, PIK3C2B, PIK3C2G, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIM1, PKHD1, PLCG1, PLCG2, PML, PMS1, PMS2, POLD1, POLE, POLH, POLQ, POT1, PPM1D, PRDM1, PRDM16, PREX2, PRF1, PRKAR1A, PRKCA, PRKD1, PRKDC, PROM2, PRSS1, PRX, PSIP1, PSMB1, PSMB10, PSMB2, PSMB5, PSMB8, PSMB9, PSMC3IP, PSPH, PTCH1, PTCH2, PTEN, PTGS2, PTK2, PTK7, PTPN11, PTPRC, PTPRD, PTPRT, RAC1, RAC2, RAD21, RAD50, RAD51, RAD51B, RAD51C, RAD51D, RAD54B, RAD54L, RAF1, RALGDS, RARA, RARB, RARG, RASA1, RASAL1, RB1, RBM10, RECQL4, REL, RET, RFC2, RFX5, RHBDF2, RHEB, RHOA, RICTOR, RINT1, RIPK1, RIT1, RNASEL, RNF2, RNF43, ROS1, RPL22, RPS20, RPS6KB1, RPTOR, RSF1, RUNX1, RYR1, SACS, SAMHD1, SAV1, SBDS, SCG5, SDHA, SDHAF2, SDHB, SDHC, SDHD, SEC23B, SEMA4A, SETBP1, SETD2, SETDB1, SF3B1, SGK1, SH2B1, SH2B3, SH2D1A, SHFM1, SHH, SIK2, SIN3A, SIRT1, SKP2, SLC26A3, SLIT2, SLX4, SMAD3, SMAD4, SMARCA4, SMARCB1, SMARCE1, SMC1A, SMC3, SMO, SOCS1, SOX11, SOX2, SOX9, SPEN, SPINK1, SPOP, SPRED1, SPTA1, SRC, SRD5A2, SRGAP1, SRP72, SRSF2, SSTR1, SSTR2, SSTR3, SSTR5, SSX1, STAG1, STAG2, STAT1, STAT3, STAT5A, STAT5B, STK11, SUFU, SUZ12, SYK, TAF1, TAF15, TAP1, TAP2, TBK1, TBL1XR1, TBX3, TCF3, TCF7L2, TCL1A, TEK, TERC, TERF2IP, TERT, TET1, TET2, TFE3, TGFBR2, TLR4, TLX1, TMEM127, TNF, TNFAIP3, TNFRSF11A, TNFRSF13B, TNFRSF14, TNFRSF1A, TNFRSF1B, TNFRSF25, TNFRSF8, TNFSF11, TNK2, TOP1, TOP2A, TP53, TP53BP1, TPX2, TRAF2, TRAF3, TRAF5, TRAF6, TRAF7, TRRAP, TSC1, TSC2, TSHR, TUBA4A, TUBB, TYMS, U2AF1, UBE2T, UBR5, UGT2B15, UGT2B7, UIMC1, UNG, USP34, USP9X, VEGFA, VEGFB, VHL, VKORC1, WAS, WASF3, WHSC1, WISP3, WRN, WT1, XIAP, XPA, XPC, XPO1, XRCC1, XRCC2, XRCC3, XRCC5, XRCC6, YAP1, ZFHX3, ZHX3, ZNF217, ZNRF3, ZRSR2

Additional detection of selected translocations in these genes
ALK, BCL2, BCR, BRAF, BRD4, EGFR, ERG, ETV4, ETV6, EWSR1, FGFR1, FGFR2, FGFR3, FUS, MYB, MYC, NOTCH2, NTRK1, PAX3, PDGFB, RARA, RET, ROS1, SSX1, SUZ12, TAF15, TCF3, TFE3, TMPRSS2