Mitochondrial sites and genes associated with prostate cancer
AssigneeGenesis Genomics Inc.
InventorsMark Birch-Machin, Gabriel Dakubo, Robert Thayer, Ryan Parr
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Abstract
A cluster analysis of mutations in the mitochondrial genomes from malignant, adjacent benign and distant benign tissues from a sample of men having prostate cancer has determined that mutations in ND1, ND2, COX1 and CytB are indicative of prostate cancer. 97% (30/31) of the samples contained synonymous and non-synonymous mutations in these genes. 65% (20/31) of the samples contained non-synonymous mutations in these genes.
Claims27
Use of a synonymous or non-synonymous mutation in an ND1 nucleic acid molecule of mtDNA, to detect a predisposition to prostate cancer, early detection of prostate cancer, genesis of prostate cancer, presence of prostate cancer, or progression of prostate cancer in a subject having mtDNA.
Use of a synonymous or non-synonymous mutation in an ND2 nucleic acid molecule of mtDNA, to detect a predisposition to prostate cancer, early detection of prostate cancer, genesis of prostate cancer, presence of prostate cancer, or progression of prostate cancer in a subject having mtDNA.
Use of a synonymous or non-synonymous mutation in a COX1 nucleic acid molecule of mtDNA, to detect a predisposition to prostate cancer, early detection of prostate cancer, genesis of prostate cancer, presence of prostate cancer, or progression of prostate cancer in a subject having mtDNA.
Use of a synonymous or non-synonymous mutation in a CytB nucleic acid molecule of mtDNA, to detect a predisposition to prostate cancer, early detection of prostate cancer, genesis of prostate cancer, presence of prostate cancer, or progression of prostate cancer in a subject having mtDNA.
A method of detecting a mutation associated with prostate cancer in a subject having mtDNA, comprising:
- a. providing a biological sample from the subject, wherein the biological sample is chosen from non-involved tissue, distant benign tissue, adjacent benign tissue, atypical tissue, histologically abnormal tissue, and malignant tissue;
- b. extracting DNA from the biological sample;
- c. detecting the presence of the mutation in ND1, ND2, COX1 or CytB of mtDNA;
- and
- d. determining whether the mutation is associated with normal interpopulation or intrapopulation variations, or whether the mutation is associated with prostate cancer.
An array comprising a plurality of nucleic acid members, and a solid substrate, wherein each of the nucleic acid members is associated with at least one mutation in ND1, ND2, COX1 or CytB of the mitochondrial genome and is indicative of the presence of prostate cancer, and is chosen from mitochondrial DNA, RNA transcribed from mitochondrial DNA, and cDNA, wherein each nucleic acid member has a unique position on said array and is stably associated with the solid substrate.
An array comprising a plurality of nucleic acid members, and a solid substrate, wherein each of the nucleic acid members is associated with at least one mutation in ND1, ND2, COX1 or CytB of the mitochondrial genome and is indicative of the progression toward prostate cancer, and is chosen from mitochondrial DNA, RNA transcribed from mitochondrial DNA, and cDNA, wherein each nucleic acid member has a unique position on said array and is stably associated with the solid substrate.
A database containing mitochondrial DNA sequences for ND1, ND2, COX1 and CytB, the sequences are chosen from normal control sequences associated with non-disease states, sequences associated with interpopulation variations, sequences associated with intrapopulation variations, and sequences associated with prostate cancer.
A method of monitoring a person for the progression toward prostate cancer or progression of prostate cancer, in a biological sample from a subject, comprising:
- (a) providing a biological sample from the subject;
- (b) extracting DNA from the biological sample;
- (c) detecting the presence of mutations in the ND1, ND2, COX1 or CytB genes of the mtDNA;
- (d) determining whether the mutations are associated with normal interpopulation or intrapopulation variations, or whether the mutations are associated with presence of a predisposition to prostate cancer, progression toward prostate cancer, prostate cancer or progression of prostate cancer, and;
- (e) repeating steps (a) to (d).
An isolated mitochondrial ND1 nucleic acid molecule comprising at least one synonymous or non-synonymous mutation for use in detecting the progression toward prostate cancer or the presence of prostate cancer in a subject.
An isolated mitochondrial ND2 nucleic acid molecule comprising at least one synonymous or non-synonymous mutation for use in detecting the progression toward prostate cancer or the presence of prostate cancer in a subject.
An isolated mitochondrial COX1 nucleic acid molecule comprising at least one synonymous or non-synonymous mutation for use in detecting the progression toward prostate cancer or the presence of prostate cancer in a subject.
An isolated mitochondrial CytB nucleic acid molecule comprising at least one synonymous or non-synonymous mutation for use in detecting the progression toward prostate cancer or the presence of prostate cancer in a subject.
Dependencies are inferred from the claim text.