Whole-genome doubling (WGD)
Whole-genome doubling is a single event in which a cancer cell duplicates its entire genome, becoming tetraploid. It happens in about a third of cancers and buffers the chaos that follows.
Occurs in ~30% of tumours, often early, associated with TP53 loss; tolerates subsequent chromosome loss and CIN, accelerates evolution, and worsens prognosis. Creates dependencies (KIF18A, spindle checkpoint) being exploited by CIN-directed drugs.
Relapse after surgery is driven by particular subclones that can be identified in the primary tumour and tracked in blood, which argues for evolution-aware adjuvant strategies. The pollution finding reframes carcinogenesis: some agents promote already-mutant cells rather than causing mutations.
Lung cancers keep evolving after they form, and it is ongoing chromosomal instability rather than the number of mutations that best predicts who will relapse. This gives a rationale for targeting the earliest (clonal) drivers and neoantigens and for tracking evolution in blood after surgery.
Pages like this
not linked directly; found by shared links- CompanyBulsara Bioworks
Shares p53 / RB / cell-cycle checkpoint, TP53.
- IdeaDegrade the damaged p53 protein rather than trying to repair it
Shares p53 / RB / cell-cycle checkpoint, TP53.
- IdeaExtend p53 reactivation beyond the Y220C mutation
Shares p53 / RB / cell-cycle checkpoint, TP53.
- ProductEprenetapopt
Shares p53 / RB / cell-cycle checkpoint, TP53.
- PathwayDNA replication stress
Shares Enabling characteristic: genome instability and mutation, Chromosomal instability & aneuploidy, p53 / RB / cell-cycle checkpoint, TP53.
- PersonCharles Swanton
Shares TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse, TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse.
- InstitutionThe Francis Crick Institute
Shares Is aneuploidy itself a druggable vulnerability?, TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse, TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse, Chromosomal instability & aneuploidy.
- PathwayClonal evolution & minimal residual disease
Shares TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse, TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse, Chromosomal instability & aneuploidy, TP53.