Neuroendocrine Tumors

Abstract

The disclosure provides methods for the use of gene expression measurements to classify or identify neuroendocrine cancer in samples obtained from a subject in a clinical setting, such as in cases of formalin fixed, paraffin embedded (FFPE) samples.

What is claimed is: 
     
         1 . A method of classifying a cell containing sample as containing neuroendocrine tumor cells, said method comprising
 detection of expressed RNAs, or cDNA copies thereof, to determine the expression levels of one or more sequences selected from AY033998 (SEQ ID NO: 3) (ELAV4), BC015754 (SEQ ID NO: 4) (CADPS), BC013117 (SEQ ID NO: 12) (RGS17) and AI309080 (SEQ ID NO: 9) (KCNJ11) in cancer cells of a sample obtained from a human subject,   comparison of said expression levels to expression levels of the same transcribed sequences in known neuroendocrine tumor specimens; and   classification of the sample as containing or not containing neuroendocrine tumor cells.   
     
     
         2 . The method of  claim 1  wherein said detection is of cDNA copies of said expressed RNA. 
     
     
         3 . The method of  claim 1  wherein said detection comprises amplification of the cDNA copies. 
     
     
         4 . The method of  claim 2  wherein said detection comprises sequencing of the cDNA copies. 
     
     
         5 . The method of  claim 1  wherein said detection comprises labeling said expressed RNAs before determining their expression levels. 
     
     
         6 . The method of  claim 1  wherein said detection comprises determining the expression levels of three of more sequences selected from AY033998 (SEQ ID NO: 3) (ELAV4), BC015754 (SEQ ID NO: 4) (CADPS), BC013117 (SEQ ID NO: 12) (RGS17) and AI309080 (SEQ ID NO: 9) (KCNJ11). 
     
     
         7 . The method of  claim 3  wherein said amplifying comprises amplification of all or part of the sequences, or reverse transcription and labeling RNA corresponding to said sequences. 
     
     
         8 . The method of  claim 7  wherein said amplification comprises linear RNA amplification or quantitative PCR. 
     
     
         9 . The method of  claim 8  wherein said amplification is quantitative PCR amplification of at least 50 nucleotides of the sequences. 
     
     
         10 . The method of  claim 1 , wherein said sample is a formalin fixed, paraffin embedded (FFPE) sample. 
     
     
         11 . A method of classifying a cell containing sample as containing a subtype of neuroendocrine tumor cells, said method comprising
 detection of expressed RNAs, or cDNA copies thereof, to determine the expression levels of one or more sequences in cancer cells of a sample obtained from a human subject,   comparison of said expression levels to expression levels of the same transcribed sequences in known neuroendocrine tumor specimens of adrenal-pheochromocytoma/paraganglioma, gastrointestinal neuroendocrine tumor, pulmonary carcinoid, pulmonary small cell or large cell carcinoma, pancreatic neuroendocrine tumor, Merkel cell carcinoma, and medullary thyroid carcinoma; and   classification of the sample as containing or a neuroendocrine tumor selected from adrenal-pheochromocytoma/paraganglioma, gastrointestinal neuroendocrine tumor, pulmonary carcinoid, pulmonary small cell or large cell carcinoma, pancreatic neuroendocrine tumor, Merkel cell carcinoma, and medullary thyroid carcinoma.   
     
     
         12 . The method of  claim 11 , wherein the one or more sequences are selected from BC008764 (SEQ ID NO: 8), AK027147 (SEQ ID NO: 5), BC002551 (SEQ ID NO: 17), BC010626 (SEQ ID NO: 11), NM — 004063 (SEQ ID NO: 13), BE552004 (SEQ ID NO: AK054605 (SEQ ID NO: 6), AW194680 (SEQ ID NO: 10), BC012926 (SEQ ID NO: 14), AI804745 (SEQ ID NO: 7), AI685931 (SEQ ID NO: 15), BF437393 (SEQ ID NO: 1), AL039118 (SEQ ID NO: 18), H09748 (SEQ ID NO: 16), and BF224381 (SEQ ID NO: 2) in cancer cells of a sample obtained from a human subject, and said detection is optionally of cDNA copies of the sequences. 
     
     
         13 . The method of  claim 11  wherein said detection is of cDNA copies of said expressed RNA. 
     
     
         14 . The method of  claim 13  wherein said detection comprises amplification of the cDNA copies, optionally further comprising sequencing of the cDNA copies. 
     
     
         15 . The method of  claim 11  wherein said detection comprises labeling said expressed RNAs before determining their expression levels. 
     
     
         16 . The method of  claim 11  wherein said detection comprises determining the expression levels of five or more sequences selected from BC008764 (SEQ ID NO: 8), AK027147 (SEQ ID NO: 5), BC002551 (SEQ ID NO: 17), BC010626 (SEQ ID NO: NM — 004063 (SEQ ID NO: 13), BE552004 (SEQ ID NO: 19), AK054605 (SEQ ID NO: 6), AW194680 (SEQ ID NO: 10), BC012926 (SEQ ID NO: 14), AI804745 (SEQ ID NO: 7), AI685931 (SEQ ID NO: 15), BF437393 (SEQ ID NO: 1), AL039118 (SEQ ID NO: 18), H09748 (SEQ ID NO: 16), and BF224381 (SEQ ID NO: 2). 
     
     
         17 . The method of  claim 14  wherein said amplifying comprises amplification of all or part of the sequences, or reverse transcription and labeling RNA corresponding to said sequences. 
     
     
         18 . The method of  claim 17  wherein said amplification comprises linear RNA amplification or quantitative PCR, optionally of at least 50 nucleotides of the sequences. 
     
     
         19 . The method of  claim 11  wherein said sample is a formalin fixed, paraffin embedded (FFPE) sample. 
     
     
         20 . A kit comprising one or more reagents for the practice of a method of  claim 1 , optionally comprising directions for the performance of the method.