What is Immortality and instability?

Normal somatic cells lack telomerase and count their divisions in telomere length (Chapter 24): after some fifty they senesce, and a cell that bypasses senescence by losing p53 and Rb goes on until its telomeres are exhausted and its chromosomes fuse and break — a crisis that kills most clones. The rare survivor has reactivated telomerase, usually by a promoter mutation, and is immortal; $90\,\%$ of cancers express the enzyme. The crisis leaves scars: fused and broken chromosomes, amplifications, deletions, translocations — chromosomal instability, which, with the loss of the spindle checkpoint and of p53’s response to missegregation, makes most solid tumours aneuploid and keeps them generating variants. A minority of tumours instead have a mutator phenotype from lost mismatch repair, with a normal karyotype and a thousandfold point-mutation rate.