Methods for subtyping of head and neck squamous cell carcinoma
AssigneesGeneCentric Therapeutics, Inc., The University of North Carolina at Chapel Hill
InventorsMyla Lai-Goldman, Hawazin Faruki, Greg Mayhew, Charles Perou, David Neil Hayes
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Abstract
Methods and compositions are provided for determining a subtype of head and neck squamous cell carcinoma (HNSCC) of an individual by detecting the expression level of at least one classifier biomarker selected from a group of gene signatures for HNSCC. Also provided herein are methods and compositions for determining the response of an individual with a HNSCC subtype to a therapy such as immunotherapy.
Claims15
A method of detecting a group of biomarkers in a head and neck tissue sample obtained from a patient, the method comprising measuring the nucleic acid expression level of every biomarker in the group of biomarkers consisting of only ATP binding cassette subfamily C member 1 (ABCC1), ATP binding cassette subfamily C member 5 (ABCC5), actinin alpha 1 (ACTN1), amyloid beta precursor protein binding family B member 2 (APBB2), apolipoprotein L3 (APOL3), aquaporin 3 (AQP3), ATPase 13A4 (ATP13A4), ATPase H+ transporting V1 subunit D (ATP6V1D), calcium binding tyrosine phosphorylation regulated (CABYR), caspase 4 (CASP4), caveolin 1 (CAV1), corneodesmosin (CDSN), choline phosphotransferase 1 (CHPT1), carbohydrate sulfotransferase 7 (CHST7), class II major histocompatibility complex transactivator (CIITA), CKLF like MARVEL transmembrane domain containing 3 (CMTM3), collagen type VI alpha 1 chain (COL6A1), collagen type VI alpha 2 chain (COL6A2), cystatin A (CSTA), Cytochrome P450 family 26 subfamily A member 1 (CYP26A1), dehydrogenase/reductase 1 (DHRS1), E74 like ETS transcription factor 3 (ELF3), epithelial cell adhesion molecule (EPCAM), epithelial mitogen (EPGN), family with sequence similarity 171 member A1 (FAM171A1), family with sequence similarity 3 member B (FAM3B), striatin interacting protein 1 (FAM40A), filamin binding LIM protein 1 (FBLIM1), forkhead box A1 (FOXA1), follistatin like 3 (FSTL3), fucosyltransferase 6 (FUT6), glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (I blood group) (GCNT2), glutathione peroxidase 8 (putative) (GPX8), grainyhead like transcription factor 3 (GRHL3), gasdermin A (GSDMA), HLF, PAR bZIP transcription factor (HLF), interleukin 4 receptor (IL4R), inhibin beta A subunit (INHBA), KIAA1609, Kruppel like factor 5 (KLF5), prolyl 3-hydroxylase 1 (LEPRE1), latent transforming growth factor beta binding protein 3 (LTBP3), mal, T-cell differentiation protein 2 (MAL2), MAP7 domain containing 1 (MAP7D1), Meis homeobox 1 (MEIS1), MOB kinase activator 3B (MOBKL2B), mucin 4, cell surface associated (MUC4), nicotinamide N-methyltransferase (NNMT), NOP2/Sun RNA methyltransferase family member 7 (NSUN7), olfactomedin like 2B (OLFML2B), olfactomedin like 3 (OLFML3), prolyl 4-hydroxylase, transmembrane (P4HTM), POZ/BTB and AT hook containing zinc finger 1 (PATZ1), PBX homeobox 1 (PBX1), procollagen C-endopeptidase enhancer (PCOLCE), pleckstrin homology like domain family B member 1 (PHLDB1), placenta specific 8 (PLAC8), phospholipase D2 (PLD2), peroxisome proliferator activated receptor delta (PPARD), periplakin (PPL), protein kinase, X-linked (PRKX), RAB6B, member RAS oncogene family (RAB6B), ribosomal modification protein rimK like family member A (RIMKLA), serpin family E member 1 (SERPINE1), serpin family H member 1 (SERPINH1), sideroflexin 3 (SFXN3), SH3-containing guanine nucleotide exchange factor (SGEF), solute carrier family 31 member 2 (SLC31A2), SLC9A3 regulator 1 (SLC9A3R1), snail family transcriptional repressor 2 (SNAI2), transforming growth factor beta induced (TGFBI), tight junction protein 3 (TJP3), transmembrane protein 51 (TMEM51), transmembrane protease, serine 11A (TMPRSS11A), transmembrane protease, serine 11B (TMPRSS11B), transmembrane protease, serine 2 (TMRSS2), tetratricopeptide repeat domain 9 (TTC9), thioredoxin reductase 1 (TXNRD1), ubiquitin like modifier activating enzyme 7 (UBA7) and zinc finger DHHC-type containing 2 (ZDHHC2) in the head and neck tissue sample obtained from the patient using an amplification, a hybridization and/or a sequencing assay.
A method of treating HNSCC in a patient, the method comprising:
- (a) determining the subtype of a head and neck tissue sample obtained from the patient, wherein the determining the subtype comprises:
- (i) measuring the nucleic acid expression level of every biomarker in a group of biomarkers in the head and neck tissue sample obtained from the patient, wherein the group of biomarkers consists of only ABCC1, ABCC5, ACTN1, APBB2, APOL3, AQP3, ATP13A4, ATP6V1D, CABYR, CASP4, CAV1, CDSN, CHPT1, CHST7, CIITA, CMTM3, COL6A1, COL6A2, CSTA, CYP26A1, DHRS1, ELF3, EPCAM, EPGN, FAM171A1, FAM3B, FAM40A, FBLIM1, FOXA1, FSTL3, FUT6, GCNT2, GPX8, GRHL3, GSDMA, HLF, IL4R, INHBA, KIAA1609, KLF5, LEPRE1, LTBP3, MAL2, MAP7D1, MEIS1, MOBKL2B, MUC4, NNMT, NSUN7, OLFML2B, OLFML3, P4HTM, PATZ1, PBX1, PCOLCE, PHLDB1, PLAC8, PLD2, PPARD, PPL, PRKX, RAB6B, RIMKLA, SERPINE1, SERPINH1, SFXN3, SGEF, SLC31A2, SLC9A3R1, SNAI2, TGFBI, TJP3, TMEM51, TMPRSS11A, TMPRSS11B, TMRSS2, TTC9, TXNRD1, UBA7 and ZDHHC2;
- (ii) comparing the detected nucleic acid expression levels of ABCC1, ABCC5, ACTN1, APBB2, APOL3, AQP3, ATP13A4, ATP6V1D, CABYR, CASP4, CAV1, CDSN, CHPT1, CHST7, CIITA, CMTM3, COL6A1, COL6A2, CSTA, CYP26A1, DHRS1, ELF3, EPCAM, EPGN, FAM171A1, FAM3B, FAM40A, FBLIM1, FOXA1, FSTL3, FUT6, GCNT2, GPX8, GRHL3, GSDMA, HLF, IL4R, INHBA, KIAA1609, KLF5, LEPRE1, LTBP3, MAL2, MAP7D1, MEIS1, MOBKL2B, MUC4, NNMT, NSUN7, OLFML2B, OLFML3, P4HTM, PATZ1, PBX1, PCOLCE, PHLDB1, PLAC8, PLD2, PPARD, PPL, PRKX, RAB6B, RIMKLA, SERPINE1, SERPINH1, SFXN3, SGEF, SLC31A2, SLC9A3R1, SNAI2, TGFBI, TJP3, TMEM51, TMPRSS11A, TMPRSS11B, TMRSS2, TTC9, TXNRD1, UBA7 and ZDHHC2 in the head and neck tissue sample obtained from the patient to the nucleic acid expression levels of ABCC1, ABCC5, ACTN1, APBB2, APOL3, AQP3, ATP13A4, ATP6V1D, CABYR, CASP4, CAV1, CDSN, CHPT1, CHST7, CIITA, CMTM3, COL6A1, COL6A2, CSTA, CYP26A1, DHRS1, ELF3, EPCAM, EPGN, FAM171A1, FAM3B, FAM40A, FBLIM1, FOXA1, FSTL3, FUT6, GCNT2, GPX8, GRHL3, GSDMA, HLF, IL4R, INHBA, KIAA1609, KLF5, LEPRE1, LTBP3, MAL2, MAP7D1, MEIS1, MOBKL2B, MUC4, NNMT, NSUN7, OLFML2B, OLFML3, P4HTM, PATZ1, PBX1, PCOLCE, PHLDB1, PLAC8, PLD2, PPARD, PPL, PRKX, RAB6B, RIMKLA, SERPINE1, SERPINH1, SFXN3, SGEF, SLC31A2, SLC9A3R1, SNAI2, TGFBI, TJP3, TMEM51, TMPRSS11A, TMPRSS11B, TMRSS2, TTC9, TXNRD1, UBA7 and ZDHHC2 in at least one sample training set, wherein the at least one sample training set comprises a reference HNSCC BA sample, a reference HNSCC MS sample, a reference HNSCC AT sample, a reference HNSCC CL sample or a combination thereof;
- and
- (iii) classifying the sample as basal (BA), mesenchymal (MS), atypical (AT) or classical (CL) based on the results of the comparing step;
- and
- (b) administering an immunotherapeutic agent based on the subtype of the HNSCC.
Dependencies are inferred from the claim text.