Researchers in UCLA Department of Human Genetics have developed a novel method of using the mitochondrial genome of prostate cancer patients to predict which tumours are likely to become lethal.
BACKGROUND:
Prostate cancer remains the most prevalent non-skin cancer in men. Most studies of the prostate cancer genome focused on mutations in the nuclear genome, yet have not identified highly recurrent driver non-coding somatic single nucleotide variants (SNVs) or genomic rearrangements. Despite these failures, exhaustive studies have tried to identify mutations that might be useful in guiding clinical decision-making. By contrast, the second genome of the human cell, the mitochondrial genome, has historically been ignored. It remains an urgent clinical need to identify ways to identify which prostate tumours are most likely to kill patients so that those men can receive the intensive life-preserving therapies they need.
INNOVATION:
Researchers in UCLA Department of Human Genetics have developed a novel method of prognosing the progression of prostate cancer in patients from biomarker signatures in the mitochondrial DNA. Four specific mitochondrial single nucleotide variations (mtSNVs) were determined from sequencing the mitochondrial genomes of 384 localized prostate cancer patients that are significantly associated with biochemical relapse rates. As few as three mtSNVs were sufficient to successfully indicate patients’ risk of biochemical failure independent of clinical features, and an optimal signature of seven mtSNVs was created and validated.
POTENTIAL APPLICATIONS:
• New tool for prostate cancer prognosis
• Reference for patient’s risk of biochemical failure
• Cancer genome researches and drug development
ADVANTAGES:
• Similar distribution of mtSNVs in patients both younger and older than 50
• Significantly association with biochemical relapse rates
• Identified biomarkers for both better and worse patient outcome
• Bypasses intensely patented nuclear genome space, maximizing FTO
DEVELOPMENT-TO-DATE:
Biomarkers cross-validated among patient groups in tumours from two countries.
RELATED PAPERS:
Hopkins, Julia F., et al., Mitochondrial mutations drive prostate cancer aggression. Nature Communications 8, 1 (2017).