Gene fusions and gene variants associated with cancer

Abstract

The disclosure provides gene fusions, gene variants, and novel associations with disease states, as well as kits, probes, and methods of using the same.

What is claimed: 
     
         1 . A method of detecting bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma in a sample, the method comprising:
 amplifying a nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328; and   detecting the presence of the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328;   wherein detecting the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328, indicates that bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma present in the sample.   
     
     
         2 . The method of  claim 1 , wherein a gene fusion from Table 4-6, 20, 23, 42 or 49 is detected. 
     
     
         3 . The method of  claim 1 , wherein a gene variant from Table 7, 11, 41, 44, 45, 46, or 47 is detected. 
     
     
         4 . The method of  2 , wherein a gene fusion partner is two genes chosen from: TPM1 and ALK, PRKAR1A and ALK, NCOA1 and ALK, LPP and CASR, MDM2 and EGFR, FGFR3 and ELAVL3, B2M and GNAS, DOCK8 and JAK2, HNF1B and NOTCH1, NFASC and NTRK1, SSBP2 and NTRK1, SQSTM1 and NTRK1, TBL1XR1 and PIK3CA, AKAP13 and RET, FKBP15 and RET, TBL1XR1 and RET, CEP85L and ROS1, CLCN6 and RAF1, TRAK1 and RAF1, PRKACA and AKT1, PRKACA and AKT2, MLL and FYN, and TTC13 and JAK2, SEC16A and NOTCH1, ERC1 and RET, GTF21RD1 and ALK, HTATSF1 and BRS3, CDH1 and CCDC132, CCDC132 and CDH1, ERBB2 and SLC29A3, MET and TFG; TFG and MET, NOTCH2 and MNDA, IRF2BP2 and NTRK1, EIF2C2 and PTK2, RARA and HOXB3, STAT3 and ETV4, and GFAP and VIM, VIM and GFAP, TOP1 and C17orf64, and TP53 and KIAA0753. 
     
     
         5 . The method of  claim 1 , wherein the sample is a patient sample. 
     
     
         6 . The method of  claim 5 , further comprising diagnosing the patient as having bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma when a nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328 is present in the sample. 
     
     
         7 . The method of  claim 6 , further comprising administering to a patient with a gene fusion a drug, wherein the gene fusion is disclosed in Table 4-6, 20, 23, 42 or 49. 
     
     
         8 . A method of detecting a cancer in a sample, the method comprising use of a set of probes for:
 amplifying a nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328; and   detecting the presence of the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328;   wherein detecting the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328, indicates that a cancer is present in the sample.   
     
     
         9 . The method of  claim 8 , wherein detecting the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328 indicates that bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma is present in the sample. 
     
     
         10 . The method of  claim 9 , wherein a gene fusion from Table 4-6, 20, 23, 42 or 49 and/or a gene variant from Table 41, 44, 45, 46, or 47 is detected. 
     
     
         11 . The method of  10 , wherein a gene fusion partner is two genes chosen from: TPM1 and ALK, PRKAR1A and ALK, NCOA1 and ALK, LPP and CASR, MDM2 and EGFR, FGFR3 and ELAVL3, B2M and GNAS, DOCKS and JAK2, HNF1B and NOTCH1, NFASC and NTRK1, SSBP2 and NTRK1, SQSTM1 and NTRK1, TBL1XR1 and PIK3CA, AKAP13 and RET, FKBP15 and RET, TBL1XR1 and RET, CEP85L and ROSI, CLCN6 and RAFI, TRAK1 and RAFI, PRKACA and AKT1, PRKACA and AKT2, MLL and FYN, and TTC13 and JAK2, SEC16A and NOTCH1, ERC1 and RET, GTF21RD1 and ALK, HTATSF1 and BRS3, CDH1 and CCDC132, CCDC132 and CDH1, ERBB2 and SLC29A3, MET and TFG; TFG and MET, NOTCH2 and MNDA, IRF2BP2 and NTRK1, EIF2C2 and PTK2, RARA and HOXB3, STAT3 and ETV4, and GFAP and VIM, VIM and GFAP, TOP1 and
 C17orf64, and TP53 and KIAA0753.   
     
     
         12 . The method of  claim 8 , wherein the sample is a patient sample, and wherein the method further comprises diagnosing the patient as having sarcoma, bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma when a nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328 is present in the patient sample. 
     
     
         13 . The method of  claim 12 , further comprising treating the patient comprising administering to a patient with a gene fusion and/or a gene variant a drug, wherein the gene fusion from Table 4-6, 20, 23, 42 or 49 and/or the gene variant from Table 41, 44, 45, 46, or 47 is detected. 
     
     
         14 . A method of detecting sarcoma in a sample, the method comprising use of a set of probes for:
 amplifying a nucleic acid comprising SEQ ID NO: 272; and   detecting the presence of the nucleic acid comprising SEQ ID NO: 272;   wherein the set of probes specifically recognizes a fusion between the KANK2 gene and the ALK gene, and   wherein detecting the nucleic acid comprising SEQ ID NO: 272, indicates that sarcoma is present in the sample.   
     
     
         15 . The method of  claim 14 , the method additionally comprising: amplifying a nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328; and detecting the presence of the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328;
 wherein detecting the nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328, indicates that bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma is present in the sample.   
     
     
         16 . The method of  claim 15 , wherein a gene fusion from Table 4-6, 20, 23, 42 or 49 and/or a gene variant from Table 41, 44, 45, 46, or 47 is detected. 
     
     
         17 . The method of  15 , wherein a gene fusion partner is two genes chosen from: TPM1 and ALK, PRKAR1A and ALK, NCOA1 and ALK, LPP and CASR, MDM2 and EGFR, FGFR3 and ELAVL3, B2M and GNAS, DOCKS and JAK2, HNF1B and NOTCH1, NFASC and NTRK1, SSBP2 and NTRK1, SQSTM1 and NTRK1, TBL1XR1 and PIK3CA, AKAP13 and RET, FKBP15 and RET, TBL1XR1 and RET, CEP85L and ROSI, CLCN6 and RAFI, TRAK1 and RAFI, PRKACA and AKT1, PRKACA and AKT2, MLL and FYN, and TTC13 and JAK2, SEC16A and NOTCH1, ERC1 and RET, GTF21RD1 and ALK, HTATSF1 and BRS3, CDH1 and CCDC132, CCDC132 and CDH1, ERBB2 and SLC29A3, MET and TFG; TFG and MET, NOTCH2 and MNDA, IRF2BP2 and NTRK1, EIF2C2 and PTK2, RARA and HOXB3, STAT3 and ETV4, and GFAP and VIM, VIM and GFAP, TOP1 and
 C17orf64, and TP53 and KIAA0753.   
     
     
         18 . The method of  claim 15 , wherein the sample is a patient sample. 
     
     
         19 . The method of  claim 18 , further comprising diagnosing the patient as having sarcoma, bladder urothelial carcinoma, breast carcinoma, endometrial endometrioid adenocarcinoma, colon adenocarcinoma, glioblastoma multiforme, clear cell renal cell carcinoma, papillary renal cell carcinoma, acute myeloid leukemia, brain lower grade glioma, lung adenocarcinoma, ovarian serous cystadenocarcinoma, prostate adenocarcinoma, rectal cutaneous melanoma, thyroid gland carcinoma, esophageal carcinoma, hepatocellular carcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, cervical squamous cell carcinoma, or squamous cell lung carcinoma when a nucleic acid comprising a sequence selected from SEQ ID NOs: 1-328 is present in the patient sample. 
     
     
         20 . The method of  claim 8 , further comprising treating the patient comprising administering to a patient with a gene fusion and/or a gene variant a drug, wherein the gene fusion from Table 4-6, 20, 23, 42 or 49 and/or the gene variant from Table 41, 44, 45, 46, or 47 is detected.