Enabling Replicative Immortality Module

A conserved mechanism module for the fourth hallmark of cancer (Hanahan & Weinberg): the acquisition of unlimited replicative potential. Normal somatic cells can complete only a finite number of divisions because telomeres - the protective repeat caps on chromosome ends - shorten with each round of DNA replication, eventually triggering replicative senescence or crisis. This telomere clock is a powerful tumor-suppressive barrier. The conserved causal chain runs from progressive telomere attrition during clonal expansion through a proliferative crisis, to reactivation of a telomere-maintenance mechanism - in the great majority of cancers, transcriptional reactivation of the telomerase reverse transcriptase (TERT; via TERT promoter mutation, amplification, or rearrangement), and in a minority the recombination-based alternative lengthening of telomeres (ALT) - which stabilizes telomere length and confers unlimited proliferative capacity (replicative immortality). Individual disorder entries declare conformance via conforms_to, substituting the tumor-type-specific telomere-maintenance route (e.g., TERT promoter mutations in melanoma and glioblastoma, ALT in ATRX/DAXX-mutant tumors). This module is the immortality-enabling counterpart of the tumor-suppressive senescence captured in cellular_senescence and senescence_tumor_suppression.