US2011160086A1PendingUtilityA1

Gene expression signature for classification of kidney tumors

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Assignee: ROSETTA GENOMICS LTDPriority: Aug 6, 2008Filed: Aug 5, 2009Published: Jun 30, 2011
Est. expiryAug 6, 2028(~2.1 yrs left)· nominal 20-yr term from priority
Inventors:Nitzan RosenfeldYael SpectorEddie FriedmanZohar Dotan
C12Q 1/6886C12Q 1/68C12Q 2600/112C12Q 2600/158C12Q 2600/178C12Q 2600/118
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Claims

Abstract

The present invention provides a method for classification of kidney tumors through the analysis of the expression patterns of specific microRNAs and nucleic acid molecules relating thereto. Classification according to a microRNA expression framework allows optimization of treatment, and determination of specific therapy.

Claims

exact text as granted — not AI-modified
1 . A method for the detection of a specific subtype of kidney tumor, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining an expression profile in said sample of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-75, or a sequence having at least about 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby an altered expression levels of the nucleic acid sequence allows the detection of the specific subtype of kidney tumor in said sample.   
     
     
         2 . The method of  claim 1 , wherein said specific subtype is selected from the group consisting of oncocytoma, clear cell RCC (conventional), papillary (chromaphil) RCC and chromophobe RCC. 
     
     
         3 . The method of  claim 1 , wherein said altered expression level is a change in a score based on a combination of expression levels of said nucleic acid sequences. 
     
     
         4 . A method for distinguishing between benign and malignant kidney tumor, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-27, 47, 49, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said kidney tumor.   
     
     
         5 . The method of  claim 4 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 12-15, 18, 19, 25-27 is indicative of the presence of benign kidney tumor. 
     
     
         6 . The method of  claim 4 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-11, 16, 17, 20-24, 47, 49 is indicative of the presence of malignant kidney tumor. 
     
     
         7 . A method for distinguishing between chromophobe RCC and oncocytoma, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 14-15, 28-35, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value; whereby a relative abundance of said nucleic acid sequences allows the detection of said oncocytoma or chromophobe RCC.   
     
     
         8 . The method of  claim 7 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 14-15, 28-31, is indicative of the presence of oncocytoma. 
     
     
         9 . The method of  claim 7 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 32-35 is indicative of the presence of chromophobe RCC. 
     
     
         10 . A method for distinguishing between clear cell RCC and oncocytoma, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-3, 6, 7, 11, 13, 16, 17, 19-27, 30, 31, 36-40, 47-49, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said oncocytoma or clear cell RCC.   
     
     
         11 . The method of  claim 10 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NO: 13, 19, 25-27, 30, 31, 36-40, 48 is indicative of the presence of oncocytoma. 
     
     
         12 . The method of  claim 10 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-3, 6, 7, 11, 16, 17, 20-24, 47, 49 is indicative of the presence of clear cell RCC. 
     
     
         13 . A method for distinguishing between chromophobe RCC and clear cell RCC, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-3, 6, 7, 22, 23, 32-37, 43, 44, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said RCC.   
     
     
         14 . The method of  claim 13 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-3, 6, 7, 22, 23 is indicative of the presence of clear cell RCC. 
     
     
         15 . The method of  claim 13 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 32-37, 43, 44 is indicative of the presence of chromophobe RCC. 
     
     
         16 . A method for distinguishing between clear cell RCC and chromaphil RCC, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 4, 5, 8, 9, 30, 31, 41, 42, 50, 51, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said RCC.   
     
     
         17 . The method of  claim 16 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 41, 42 is indicative of the presence of clear cell RCC. 
     
     
         18 . The method of  claim 16 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 4, 5, 8, 9, 30, 31, 50, 51, is indicative of the presence of papillary (chromaphil) RCC. 
     
     
         19 . A method for distinguishing between chromophobe RCC and papillary (chromaphil) RCC, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-5, 8-11, 13, 24-27, 30-35, 43, 44, 47, 49, 52, 53, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said RCC.   
     
     
         20 . The method of  claim 19 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 13, 25-27, 32-35, 43, 44, 52, 53, is indicative of the presence of chromophobe RCC. 
     
     
         21 . The method of  claim 19 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 1-5, 8-11, 24, 30, 31, 47, 49 is indicative of the presence of papillary RCC. 
     
     
         22 . A method for distinguishing between papillary RCC and oncocytoma, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 4, 5, 8-13, 25-27, 41-42, 45-47, a fragment thereof or a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said papillary RCC or oncocytoma.   
     
     
         23 . The method of  claim 22 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 4, 5, 8-11, 45-47 is indicative of the presence of papillary RCC. 
     
     
         24 . The method of  claim 22 , wherein a relative abundance of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 12, 13, 25-27, 41-42 is indicative of the presence of oncocytoma. 
     
     
         25 . A method for distinguishing between chromophobe RCC, clear cell RCC, papillary RCC and oncocytoma, the method comprising:
 (a) obtaining a biological sample from a subject;   (b) determining in said sample an expression profile of nucleic acid sequences selected from the group consisting of SEQ ID NOS: 4, 5, 13-15, 20, 21, 25, 34, 35, 41, 42; a fragment thereof and a sequence having at least 80% identity thereto; and   (c) comparing said expression profile to a reference value;   whereby a relative abundance of said nucleic acid sequences allows the detection of said RCC.   
     
     
         26 . The method of  claim 1 , wherein said biological sample is selected from the group consisting of bodily fluid, a cell line and a tissue sample. 
     
     
         27 . The method of  claim 26 , wherein said tissue is a fresh, frozen, fixed, wax-embedded or formalin fixed paraffin-embedded (FFPE) tissue. 
     
     
         28 . The method of  claim 26 , wherein said tissue sample is a kidney tumor sample. 
     
     
         29 . The method of  claim 1 , wherein the expression levels are determined by a method selected from the group consisting of nucleic acid hybridization, nucleic acid amplification, and a combination thereof. 
     
     
         30 . The method of  claim 29 , wherein the nucleic acid hybridization is performed using a solid-phase nucleic acid biochip array. 
     
     
         31 . The method of  claim 29 , wherein the nucleic acid hybridization is performed using in situ hybridization. 
     
     
         32 . The method of  claim 31 , wherein the in situ hybridization method comprises hybridization with a probe. 
     
     
         33 . The method of  claim 32 , wherein the probe comprises a nucleic acid sequence that is complementary to a sequence selected from the group consisting of SEQ ID NOS: 1-75 and sequences at least about 80% identical thereto. 
     
     
         34 . The method of  claim 29 , wherein the nucleic acid amplification method is real-time PCR(RT-PCR). 
     
     
         35 . The method of  claim 34 , wherein the RT-PCR method comprises forward and reverse primers. 
     
     
         36 . The method of  claim 35 , wherein the forward primer comprises a sequence selected from the group consisting of SEQ 11) NOS: 82-87, a fragment thereof and sequences at least about 80% identical thereto. 
     
     
         37 . The method of  claim 35 , wherein the reverse primer comprises SEQ ID NO: 90, a fragment thereof and sequences at least about 80% identical thereto. 
     
     
         38 . The method of  claim 35 , wherein the RT-PCR method further comprises hybridization with a probe. 
     
     
         39 . The method of  claim 38 , wherein the probe comprises a nucleic acid sequence that is complementary to a sequence selected from the group consisting of SEQ ID NOS: 1-75, a fragment thereof and sequences at least about 80% identical thereto. 
     
     
         40 . The method of  claim 39 , wherein the probe comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 76-81, a fragment thereof and sequences at least about 80% identical thereto. 
     
     
         41 . A kit for renal tumor classification, said kit comprises a probe comprising a nucleic acid sequence that is complementary to a sequence selected from the group consisting of SEQ ID NOS: 1-75, a fragment thereof and sequences having at least about 80% identity thereto. 
     
     
         42 . The kit of  claim 41 , wherein the probe comprising a nucleic acid sequence that is complementary to a sequence selected from the group consisting of
 SEQ ID NOS: 76-81, a fragment thereof and sequences at least about 80% identical thereto.   
     
     
         43 . The kit of  claim 41 , further comprises forward and reverse primers. 
     
     
         44 . The kit of  claim 43 , wherein the forward primer comprising a sequence selected from the group consisting of SEQ ID NOS: 82-87, a fragment thereof and sequences having at least about 80% identity thereto. 
     
     
         45 . The kit of  claim 43 , wherein the reverse primer comprises SEQ ID NO: 90, a fragment thereof and sequences having at least about 80% identity thereto. 
     
     
         46 . The kit of  claim 41 , wherein the kit comprises reagents for performing in situ hybridization analysis.

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