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The prostate cancers with a broken proofreading system usually break it by tearing the gene apart rather than by switching it off, which is the opposite of what happens in bowel cancer.
A hypermutated subtype of advanced prostate cancer had been described but its prevalence and mechanism were not characterised. Of 60 advanced prostate cancers examined, 7, 12%, were hypermutated, and all of the hypermutated cancers had mismatch repair gene mutations and microsatellite instability. The mutations were frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1 epigenetic silencing, identifying both parallels and differences with the mechanisms of hypermutation in other microsatellite instability-associated cancers.
It matters for how the test is done. A mismatch repair assay designed around the colorectal mechanism, looking for MLH1 promoter methylation and simple mutations, can miss the prostate mechanism entirely, which is one reason microsatellite instability was under-recognised in this disease for so long.
Shares MSH6, MSH2, MSI-high (microsatellite instability by PCR or sequencing), Lynch syndrome.
Shares MSH2, MSI-high (microsatellite instability by PCR or sequencing), Lynch syndrome, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).
Shares MSH6, MSH2, MSI-high (microsatellite instability by PCR or sequencing), Lynch syndrome.
Shares MSH6, MSH2, MSI-high (microsatellite instability by PCR or sequencing), Lynch syndrome.
Shares MSH2, DNA damage response & homologous recombination, Lynch syndrome, Mismatch repair & microsatellite instability.
Shares MSI-high (microsatellite instability by PCR or sequencing), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Whole-exome & whole-genome sequencing.
Shares MSI-high (microsatellite instability by PCR or sequencing), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Whole-exome & whole-genome sequencing.
Shares MSI-high (microsatellite instability by PCR or sequencing), Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Whole-exome & whole-genome sequencing.
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