Materials and methods for assessing progression of prostate cancer

Abstract

Methods of distinguishing and identifying a patient with aggressive/indolent, prostatic adenocarcinoma comprising contacting a sample from the patient with a set of detectably labeled probes under hybridization conditions and determining the presence of chromosomal abnormalities in the sample; sets of probes for use in such methods; and kits comprising a set of probes and instructions for distinguishing or identifying a patient as having aggressive/indolent, prostatic adenocarcinoma.

1 .- 25 . (canceled) 
     
     
         26 . A set of distinctly, detectably labeled probes consisting of a locus specific probe for CMYC, a break-apart probe for ERG, a locus-specific probe for FGFR1, and either (i) a locus-specific probe for PTEN or (ii) a locus-specific probe for MYCN. 
     
     
         27 . The set of  claim 26 , which consists of a locus-specific probe for PTEN. 
     
     
         28 . The set of  claim 26 , which consists of a locus-specific probe for MYCN. 
     
     
         29 . A kit consisting of:
 (a) a set of distinctly, detectably labeled probes that enables identification of a patient with aggressive, prostatic adenocarcinoma, wherein the set of probes consists of a locus specific probe for CMYC, a break-apart probe for ERG, a locus-specific probe for FGFR1, and either (i) a locus-specific probe for PTEN or (ii) a locus-specific probe for MYCN;   (b) instructions for identifying a patient with a high risk of developing aggressive, prostatic adenocarcinoma, wherein the instructions comprise determining in a sample obtained from the patient the presence of chromosomal abnormalities, wherein one or more of (i) a copy number of the CMYC gene that is greater than 2, (ii) a duplication of an ERG gene fusion and an interstitial deletion of sequences 5′ to the ERG gene (ERG 2+Edel), (iii) a copy number of the FGFR1 gene that is less than 1, (iv) homozygous loss of the PTEN gene, and/or (v) a copy number of the MYCN gene that is greater than 2, indicates that the patient has a high risk of developing aggressive, prostatic adenocarcinoma.   
     
     
         30 . The kit of  claim 29 , which consists of a locus-specific probe for PTEN. 
     
     
         31 . The kit of  claim 29 , which consists of a locus-specific probe for MYCN. 
     
     
         32 . A method comprising determining the copy number of the CMYC, ERG, FGFR1, and either PTEN or MYCN genes in a prostate adenocarcinoma sample by:
 (a) contacting the sample with a set of detectably labeled probes consisting of a locus specific probe for CMYC, a break-apart probe for ERG, a locus-specific probe for FGFR1, and either (i) a locus-specific probe for PTEN or (ii) a locus-specific probe for MYCN; and   (b) performing fluorescence in situ hybridization.   
     
     
         33 . The method of  claim 32 , further comprising determining one or more of the Gleason score, tumor stage, and/or prostate-specific antigen (PSA) level of the prostate adenocarcinoma. 
     
     
         34 . A method of treating a prostate adenocarcinoma in a human, which method comprises:
 (a) contacting a prostate adenocarcinoma sample obtained from a human with a set of detectably labeled probes consisting of a locus specific probe for CMYC, a break-apart probe for ERG, a locus-specific probe for FGFR1, and either (i) a locus-specific probe for PTEN or (ii) a locus-specific probe for MYCN and performing fluorescence in situ hybridization;   (b) detecting in the prostate adenocarcinoma sample one or more of (i) a copy number of the CMYC gene that is greater than 2, (ii) a duplication of an ERG gene fusion and an interstitial deletion of sequences 5′ to the ERG gene (ERG 2+Edel), (iii) a copy number of the FGFR1 gene that is less than 1, (iv) homozygous loss of the PTEN gene, and/or (v) a copy number of the MYCN gene that is greater than 2; and   (c) administering to the human one or more of surgery, hormone therapy, radiation, and/or androgen deprivation, whereupon the prostatic adenocarcinoma is treated.   
     
     
         35 . The method of  claim 34 , which comprises detecting two or more of (i) a copy number of the CMYC gene that is greater than 2, (ii) a duplication of an ERG gene fusion and an interstitial deletion of sequences 5′ to the ERG gene (ERG 2+Edel), (iii) a copy number of the FGFR1 gene that is less than 1, (iv) homozygous loss of the PTEN gene, and/or (v) a copy number of the MYCN gene that is greater than 2. 
     
     
         36 . The method of  claim 35 , which comprises detecting (i) a copy number of the CMYC gene that is greater than 2, (ii) a duplication of an ERG gene fusion and an interstitial deletion of sequences 5′ to the ERG gene (ERG 2+Edel), (iii) a copy number of the FGFR1 gene that is less than 1, and (iv) homozygous loss of the PTEN gene. 
     
     
         37 . The method of  claim 35 , which comprises detecting (i) a copy number of the CMYC gene that is greater than 2, (ii) a duplication of an ERG gene fusion and an interstitial deletion of sequences 5′ to the ERG gene (ERG 2+Edel), (iii) a copy number of the FGFR1 gene that is less than 1, and (iv) a copy number of the MYCN gene that is greater than 2. 
     
     
         38 . The method of  claim 34 , further comprising determining one or more of the Gleason score, tumor stage, prostate-specific antigen (PSA) level, and/or age of the human.