Loading
Blood DNA from 17,182 people showed that clones carrying leukaemia-associated mutations (mostly DNMT3A, TET2, ASXL1) are present in about 10% of people over 70, raising the risk of blood cancer 11-fold and, unexpectedly, of heart attack and stroke.
Exome sequences generated for diabetes genetics studies were mined for somatic mutations in genes recurrently mutated in blood cancers. Clonal haematopoiesis of indeterminate potential (CHIP) was rare under 40 but present in 9.5% of people aged 70-79 and 18.4% over 90.
Carriers had an 11-fold higher risk of subsequent haematological cancer, though the absolute rate was modest (about 0.5-1% per year). Strikingly, CHIP was associated with higher all-cause mortality (HR 1.4), driven by cardiovascular disease: coronary heart disease HR 2.0 and ischaemic stroke HR 2.6. A companion paper (Genovese, NEJM 2014) reported the same phenomenon in a Swedish cohort.
CHIP is now recognised as a common age-related premalignant state, a driver of cardiovascular inflammation, a source of false positives in ctDNA tests, and a target for prevention.
Many older people carry blood clones one or two steps from leukaemia, and those clones also drive heart disease through inflammation. CHIP is why blood-based cancer tests must filter out mutations from blood cells, and it opens a route to preventing both leukaemia and cardiovascular events in carriers.
Shares Variant allele frequency (VAF), Whole-exome & whole-genome sequencing, Circulating tumour DNA (ctDNA), The hardest cancers are found late.
Shares Variant allele frequency (VAF), Clonal evolution & minimal residual disease, Whole-exome & whole-genome sequencing, Biomarkers are not validated or standardised.
Shares Variant allele frequency (VAF), Circulating tumour DNA (ctDNA), Biomarkers are not validated or standardised, Liquid biopsy (ctDNA).
Shares Variant allele frequency (VAF), Circulating tumour DNA (ctDNA), Biomarkers are not validated or standardised, Liquid biopsy (ctDNA).
Shares Clonal evolution & minimal residual disease, Whole-exome & whole-genome sequencing, Circulating tumour DNA (ctDNA), The hardest cancers are found late.
Shares Broad Institute of MIT and Harvard, Dana-Farber Brigham Cancer Center, Whole-exome & whole-genome sequencing.
Shares Variant allele frequency (VAF), Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
Shares Clonal haematopoiesis (CHIP), Whole-exome & whole-genome sequencing, Biomarkers are not validated or standardised, Acute myeloid leukaemia.