Mitochondrial dna prostate cancer marker and related systems and methods

Abstract

There is described herein a method of prognosing and/or predicting disease progression and/or in subject with prostate cancer, the method comprising: a) providing a sample containing mitochondrial genetic material from prostate cancer cells; b) sequencing the mitochondrial genetic material with respect to at least 1 patient biomarker selected from CSB1, OHR, ATP8 and HV1 (hypervariable region 1); c) comparing the sequence of said patient biomarkers to control or reference biomarkers to determine mitochondrial single nucleotide variations (mtSNVs); and d) determining the a prostate cancer prognosis; wherein a relatively worse outcome is associated with the presence of mtSNVs in CSB1, OHR, ATP8 and a relatively better outcome is associated with the presence of mtSNVs in HV1.

1 . A method of prognosing and/or predicting disease progression and/or in subject with prostate cancer, the method comprising:
 a) providing a sample containing mitochondrial genetic material from prostate cancer cells;   b) sequencing the mitochondrial genetic material with respect to at least 1 patient biomarker selected from CSB1, OHR, ATP8 and HV1 (hypervariable region 1);   c) comparing the sequence of said patient biomarkers to control or reference biomarkers, preferably from the subject's own matched normal tissue or blood, to determine mitochondrial single nucleotide variations (mtSNVs); and   d) determining the a prostate cancer prognosis;   wherein a relatively worse outcome is associated with the presence of mtSNVs in CSB1, OHR, ATP8 and a relatively better outcome is associated with the presence of mtSNVs in HV1.   
     
     
         2 . The method according to  claim 1 , wherein the at least 1 patient biomarker, is at least 2, 3 or 4 patient biomarkers. 
     
     
         3 . The method according to  claim 1 , wherein the prostate cancer is localized prostate cancer, preferably non-indolent localized prostate cancer. 
     
     
         4 . The method according to  claim 1 , further comprising building a patient biomarker profile from the determined or measured patient biomarkers. 
     
     
         5 . The method according to  claim 1 , wherein the prostate cancer prognosis is the likelihood of disease recurrence, preferably measured by biochemical relapse. 
     
     
         6 . The method of  claim 5 , further comprising classifying the patient into a high risk group if the likelihood of disease recurrence is relatively high or a low risk group if the likelihood of disease recurrence is relatively low. 
     
     
         7 . The method of  claim 6 , further comprising treating the patient with more aggressive therapy if the patient is in the high risk group. 
     
     
         8 . The method of  claim 7 , wherein the more aggressive therapy comprises adjuvant therapy, preferably hormone therapy, chemotherapy or radiotherapy. 
     
     
         9 . The method according to  claim 1 , wherein the patient biomarkers further comprises CO2, CO3 and ND4L. 
     
     
         10 . The method of  claim 9 , wherein the at least 1 biomarker is at least 5, 6 or all 7 biomarkers. 
     
     
         11 . The method of  claim 10 , wherein the at least 1 biomarker is all 7 biomarkers. 
     
     
         12 . The method of  claim 11 , wherein the subject is classified as low risk if there exists mtSNVs in CO2, CO3, and HV1 and high risk if there exists mtSNVs in ATP8, OHR, ND4L and CSB1. 
     
     
         13 . The method according to  claim 1 , wherein the mtSNVs are the mtSNVs identified in Table 5. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . A computer program product for use in conjunction with a general-purpose computer having a processor and a memory connected to the processor, the computer program product comprising a computer readable storage medium having a computer mechanism encoded thereon, wherein the computer program mechanism may be loaded into the memory of the computer and cause the computer to carry out the method of  claim 1 . 
     
     
         16 . A computer readable medium having stored thereon a data structure for storing the computer program product according to  claim 15 . 
     
     
         17 . A device for prognosing or predicting disease progression in a patient with prostate cancer, the device comprising:
 at least one processor; and   electronic memory in communication with the at one processor, the electronic memory storing processor-executable code that, when executed at the at least one processor, causes the at least one processor to:   a) receive sequencing data of mitochondrial genetic material from prostate cancer cells of the patient, the sequencing data reflecting at least 1 patient biomarker selected from CSB1, OHR, ATP8 and HV1 (hypervariable region 1);   b) compare said sequencing data to corresponding control or reference sequences, preferably from the subject's own matched normal tissue or blood, to determine mitochondrial single nucleotide variations (mtSNVs); and   c) determining, at the at least one processor, a prostate cancer prognosis;   wherein a relatively worse outcome is associated with the presence of mtSNVs in CSB1, OHR, ATP8 and a relatively better outcome is associated with the presence of mtSNVs in HV1.   
     
     
         18 . The device according to  claim 17 , wherein the processor further displays the prostate cancer prognosis on a user display. 
     
     
         19 . A kit for prognosing or predicting disease progression in a patient with prostate cancer, the kit comprising primer sequences that permit the sequencing of a mitochondrial genome to determine mtSNVs in ATP8, OHR, ND4L and CSB1. 
     
     
         20 . The kit of  claim 19 , wherein the primers further permit sequencing of CO2, CO3 and ND4L.