Introduction
Thomas Tüting and Andreas Dominik Braun Principles of Cutaneous Tumor Biology 107
Key features
Over time, cancer genomes gradually accumulate somatic mutations, and oncogenic driver mutations that increase cell fitness are selected in a process termed Darwinian cancer evolution
Cancer evolution is also driven by complex chromosomal rearrangements (chromothripsis, chromoplexy) and mutational storms (kataegis) that occur in a single catastrophic cell division, a process called punctuated genome evolution
Oncogenic driver mutations usually activate proliferative signaling, initiate cell division, and reprogram cellular metabolism to support cell growth and proliferation
Mutations in tumor suppressor genes often deregulate cell cycle checkpoints, help cells evade physiologic mechanisms of cellular senescence and programmed cell death, and increase genome instability
By deregulating developmental signaling pathways and cell– cell communication networks, cancer cells create novel tumor ecosystems
Immune cells can sense DNA damage, specifically recognize mutated cancer cells, and enforce the adaptation and selection of cancer cell subpopulations with immune evasive phenotypes
Chromosomal instability of cancer cells and a protumorigenic inflammatory microenvironment increase cancer cell plasticity, foster epithelial–mesenchymal transitions, and enable cancer cell invasion and metastasis
Basal cell carcinomas (BCCs) arise as a result of oncogenic mutations in the Hedgehog signaling pathway, and they often have additional mutations in TP53 and the Notch pathway
Cutaneous squamous cell carcinomas (cSSCs) often carry loss-of- function mutations in the Notch pathway, TP53, and CDKN2A