Multigene analysis of tumor samples

Patent metadata

Field	Value
Publication number	US-2024327926-A1
Application number	US-202418607277-A
Country	US
Kind code	A1
Filing date	Mar 15, 2024
Priority date	Dec 5, 2014
Publication date	Oct 3, 2024
Grant date	—

Abstract

Methods of evaluating or providing a clonal profile of a subject interval, e.g., a subgenomic interval, or an expressed subgenomic interval (or of a cell containing the same), in a subject, are disclosed.

First claim

1 - 227 . (canceled)

228 . A sequencing method comprising:
(a) generating a library comprising a plurality of nucleic acids derived from a sample obtained from a subject, wherein the nucleic acid library comprises (i) a plurality of DNA molecules and (ii) a plurality of RNA molecules or cDNA molecules derived from the plurality of RNA molecules; (b) contacting the library with a bait set to provide a library catch comprising a plurality of selected nucleic acids, wherein the plurality of selected nucleic acids including at least a targeted expressed subgenomic interval associated with the RNA molecules or cDNA molecules and a targeted subgenomic interval associated with the DNA molecules, or portions thereof, wherein the bait set comprises a first portion that hybridizes to selected nucleic acids comprising the targeted expressed subgenomic interval or a portion thereof and a second portion that hybridizes to selected nucleic acids comprising the targeted subgenomic interval; and (c) sequencing the plurality of selected nucleic acids.

229 . The method of claim 228 , wherein the plurality of nucleic acid derived from the sample comprises nucleic acid fragments formed by fragmenting nucleic acid molecules from the subject.

230 . The method of claim 228 , wherein the plurality of nucleic acids derived from the sample comprises nucleic acid fragments obtained from cell-free DNA.

231 . The method of claim 228 , wherein step (b) comprises contacting the library with the bait set under conditions of solution hybridization or surface-based hybridization.

232 . The method of claim 228 , wherein the targeted subgenomic interval is chosen from a gene selected from the group consisting of ABCB1, ABCC2, ABCC4, ABCG2, ABIl, ABL1, ABL2, ACSL3, ACSL6, ACTB, ACVR1B, AF15Q14, AF1Q, AF3p21, AF5q31, AFF1, AFF4, AKAP9, AKT1, AKT2, AKT3, ALK, ALPHA, ALO17, ALOX12B, AMER1, APC, APCDD1, APH1A, AR, ARAF, ARFRP1, ARHGAP26, ARHGEF12, ARHH, ARID1A, ARIDIB, ARID2, ARNT, ASPSCR1, ASMTL, ASXL1, ATF1, ATG5, ATIC, ATM, ATR, ATRX, ATXN1, AURKA, AURKB, AXIN1, AXL, B2M, BACH1, BAP1, BARD1, BCL10, BCL11A, BCL11B, BCL2, BCL2A1, BCL2L1, BCL2L2, BCL3, BCL5, BCL6, BCL7A, BCL9, BCOR, BCORL1, BCR, BIRC3, BLM, BRAF, BRCA1, BRCA2, BRD3, BRD4, BRIP1, BRSK1, BTG1, BTG2, BTK, BTLA, clorfl44, cllorf30, cl2orf9, cl5orf21, cl7orf39, CAD, CALR, CAMTA1, CANT1, CARD11, CARS, CASP8, CBFA2T1, CBFA2T3, CBFB, CBL, CCND1, CCND2, CCND3, CCNE1, CCT6B, CD22, CD247, CD36, CD58, CD70, CD74, CD79A, CD79B, CDC73, CDH1, CDH11, CDH2, CDH20, CDH5, CDK12, CDK4, CDK6, CDK8, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CDX2, CEBPA, CEP1, CHCHD7, CHD2, CHEK1, CHEK2, CHIC2, CHN1, CHTOP, CHUK, CIC, CIITA, CKS1B, CLP1, CLTC, CLTCL1, CMKOR1, CNTRL, COL1A1, COX6C, CPS1, CRBN, CREB1, CREB3L1, CREB3L2, CREBBP, CRKL, CRLF2, CRTC3, CSF1, CSF1R, CSF3R, CTCF, CTNNA1, CTNNB1, CUL4A, CUL4B, CUX1, CXCR4, CYP1B1, CYP17A1, CYP2C19, CYP2C8, CYP2D6, CYP3A4, CYP3A5, D10S170, DAXX, DDIT3, DDR1, DDR2, DDX5, DDX10, DDX3×, DDX6, DEK, DIS3, DKC1, DLEU2, DNM2, DNMT3A, DOT1L, DPYD, DTX1, DUSP2, DUSP22, DUSP9, DUX4, EBF1, ECT2L, EED, EGFR, EIF4A2, ELF4, ELK4, ELKS, ELL, ELN, ELP2, EML4, EMSY, EP300, EPHA3, EPHA5, EPHA6, EPHA7, EPHB1, EPHB4, EPHB6, EPOR, EPS15, ERBB2, ERBB3, ERBB4, ERCC2, ERG, ESR1, ESR2, ETS1, ETV1, ETV4, ETV5, ETV6, EVI1, EWSR1, EXOSC6, EZH2, FACL6, FAF1, FAM46C, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, FANG, FANCL, FANCM, FAS, FAT3, FBXO11, FBXO31, FBXW7, FCGR2B, FCGR3A, FCRL4, FEV, FGF1, FGF10, FGF12, FGF14, FGF19, FGF23, FGF3, FGF4, FGF6, FGF7, FGFR1, FGFR1OP, FGFR2, FGFR3, FGFR4, FHIT, FIP1L1, FLCN, FLIl, FLT1, FLT3, FLT4, FLU, FLYWCH1, FNBP1, FOP, FOXL2, FOXO1, FOXO3, FOXO3A, FOXO4, FOXO1A, FOXP1, FOXP4, FRS2, FSTL3, FUS, FVT1, GADD45B, GAS7, GATA1, GATA2, GATA3, GID4, GLI1, GLIS2, GMPS, GNA11, GNA12, GNA13, GNAQ, GNAS, GOLGA5, GOPC, GPHN, GPR124, GRAF, GRIN2A, GSK3B, GSTP1, GTSE1, GUCY1A2, H4, HCMOGT-1, HDAC1, HDAC4, HDAC7, HEAB, HE110, HERPUDI, HEYl, HGF, HIP1, HISTIH1A, HISTIHIC, HISTIH1D, HISTIH1C, HIST1H2AC, HIST1H2AG, HIST1H2AL, HIST1H2AM, HIST1H2BC, HIST1H2BJ, HIST1H2BK, HIST1H2BO, HIST1H3B, HIST1H4I, HLA-A, HLF, HLXB9, HMGA1, HMGA2, HNF1A, HNRNPA2B1, HOOK3, HOX11, HOXA11, HOXA13, HOXA3, HOXA9, HOXC11, HOXC13, HOXD11, HOXD13, HRAS, HSP90AA1, HSP90AB1, HSPCA, HSPCB, ICK, ID3, IDH1, IDH2, IGF1, IGF1R, IGF2, IGF2R, IGH, IGK, IGL, IKBKE, IKZF1, IKZF2, IKZF3, IL2, IL21R, IL3, IL7R, INHBA, INPP4B, INPP5D, INSR, IRF1, IRF4, IRF8, IRS2, IRTA1, ITPA, ITK, JAK1, JAK2, JAK3, JARID2, JAZF1, JUN, KAT6A, KDM2B, KDM4C, KDM5A, KDM5C, KDM6A, KDR, KDSR, KEAP1, KIF5B, KIT, KLHL6, KIAA1549, KLK2, KMT2A, KMT2B, KMT2C, KRAS, KTN1, LAF4, LASP1, LCK, LCP1, LCX, LEF1, LHFP, LHX4, LIFR, LMO1, LMO2, LPP, LRP1B, LRP2, LRP6, LRRK2, LTK, LYL1, MAF, MAFB, MAGEA5, MAGEDI, MALTI, MAML2, MAN1B1, MAP2K1, MAP2K2, MAP2K4, MAP3K1, MAP3K13, MAP3K14, MAP3K6, MAP3K7, MECT1, MCL1, MDM2, MDM4, MDS1, MDS2, MECOM, MECT1, MED12, MEF2B, MEF2C, MEN1, MET, MHC2TA, MIB1, MITF, MKI67, MKL1, MKL2, MLF1, MLH1, MLL2, MLLT1, MLLT10, MLLT2, MLLT3, MLLT4, MLLT6, MLLT7, MLST8, MN1, MNX1, MORF, MPL, MRE11A, MSF, MSH2, MSH3, MSH6, MSI2, MSN, MTAP, MTCP1, MTHFR, MTOR, MUC1, MUTYH, MYB, MYC, MYCL, MYCL1, MYCN, MYD88, MYH11, MYH9, MYO18A, MYST3, MYST4, NACA, NBEAP1, NBN, NCOA1, NCOA2, NCOA4, NCOR1, NCOR2, NCSTN, NDRG1, NF1, NF2, NFE2L2, NFIB, NFKBIA, NFKB1, NFKB2, NFKBIE, NIN, NKX2-1, NOD1, NONO, NOTCHI, NOTCH2, NOTCH3, NOTCH4, NPM1, NQO1, NR4A3, NRP2, NRAS, NSD1, NT5C2, NTRK1, NTRK2, NTRK3, NUMA1, NUP214, NUP93, NUP98, NUT, NUTM2A, OLIG2, OMD, P2RY8, PAFAH1B2, PAG1, PAK3, PAK7, PALB2, PARP1, PARP2, PARP3, PARP4, PALB2, PASK, PAX3, PAX5, PAX7, PAX8, PBRM1, PBX1, PC, PCBP1, PCLO, PCM1, PCSK7, PDCD1, PDCD11, PDCD1LG2, PDE4DIP, PDGFB, PDGFRA, PDGFRB, PDK1, PDL1, PER1, PHF1, PHF6, PHLPP2, PHOX2B, PICALM, PIK3C2G, PIK3C3, PIK3CA, PIK3CG, PIK3R1, PIK3R2, PIM1, PKHD1, PLAG1, PLCG1, PLCG2, PML, PMS2, PMX1, PNRC1, PNUTL1, POT1, POU2AF1, POU5F1, PPARG, PPP1CB, PPP2R1A, PRCC, PRDM1, PRDM16, PRKAR1A, PRKDC, PRRX1, PRO1073, PRSS8, PSIP1, PSIP2, PTCH1, PTCH2, PTEN, PTK2, PTK2B, PTK7, PTPN11, PTPN2, PTPN6, PTPRD, PTPRO, RAB5EP, RABEPI, RAD21, RAD50, RAD51, RAD51B, RAD51C, RAD51D,RAD51L1, RAD52, RAD54L, RAF1, RALGDS, RANBP17, RAP1GDS1, RARA, RASGEFlA, RB1, RBM15, RCOR1, REL, RELN, RET, RHEB, RHOA, RHOH, RICTOR, RMRP, RNF213, RNF43, ROCK1, ROS1, RPA1, RPL11, RPL13, RPL15, RPL22, RPL35A, RPN1, RPS14, RPS15, RPS19, RPS26, RPTOR, RUNX1, RUNX1T1, RUNX2, RUNXBP2, RUNXT1, S1PR2, SBDS, SDHA, SDHB, SDHC, SDHD, SEC31A, SEPT5, SEPT6, SEPT9, SERP2, SET, SETBP1, SETD2, SF3B1, SFPQ, SFRS3, SGK1, SH2B3, SH3GL1, SIL, SLC1A2, SLC19A1, SLC22A2, SLC45A3, SLCO1B3, SMAD2, SMAD3, SMAD4, SMARCA1, SMARCA4, SMARCB1, SMARCD1, SMC1A, SMC3, SMO, SNX29, SPOP, SOCS1, SOCS2, SOCS3, SOD2, SOX10, SOX2, SPEN, SPOP, SRC, SRGAP3, SRSF2, SRSF3, SS18, SS18L1, SSH3BP1, SSX1, SSX2, SSX4, STAG2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STK11, STK12, STL, SUFU, SULTIA1, SUZ12, SYK, TAF1, TAF15, TALl, TAL2, TBL1XR1, TBX22, TBX23, TBX3, TCEA1, TCF12, TCF3, TCL1A, TCL6, TEC, TET1, TET2, TFE3, TFEB, TFG, TFPT, TFRC, TGFBR2, THRAP3, TIF1, TIPARP, TLL2, TLX1, TLX3, TMEM30A, TMPRSS2, TMSB4XP8, TNFAIP3, TNFRSF11A, TNFRSF14, TNFRSF17, TNFSF9, TNKS, TNKS2, TOP1, TP53, TP63, TPM3, TPM4, TPMT, TPR, TRA, TRAF2, TRAF3, TRAF5, TRB, TRD, TRG, TRIM24, TRIM27, TRIM33, TRIP11, TRRAP, TSC, TSC1, TSC2, TSHR, TTL, TUSC3, TYK2, TYMS, U2AF1, U2AF2, UG T1A1, UMPS, USP6, USP9×, VHL, WDR90, WHSC1, WHSC1L1, WISP3, WT1, XBP1, XPO1, XRCC3, YPEL5, YY1AP1, ZBTB16, ZMYM2, ZMYM3, ZNF145, ZNF198, ZNF217, ZNF24, ZNF278, ZNF331, ZNF384, ZNF521, ZNF703, ZNF9, ZNFN1A1, ZRSR2, and an MHC gene.

233 . The method of claim 228 , further comprising:
generating, by a sequencer, a plurality of sequence reads based on the plurality of sequenced nucleic acids; and analyzing, by a processor, the plurality of sequence reads to generate a clonal prof

Assignees

• Found Medicine Inc

Inventors

• Otto Geoffrey Alan
• Nahas Michelle
• Lipson Doron

Classifications

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12N15/1065

  Preparation or screening of tagged libraries, e.g. tagged microorganisms by STM-mutagenesis, tagged polynucleotides, gene tags · CPC title

• G16B30/10

  Sequence alignment; Homology search · CPC title

• G16B25/10

  Gene or protein expression profiling; Expression-ratio estimation or normalisation · CPC title