Hereditary cancer syndromes

Figure 1 Mechanisms of hereditary cancer predisposition. Single cancer-driving mutation is usually fully compensated, therefore carriers of germline pathogenic variants may remain healthy during a prolonged period of time. However, since every cell in the target organ already contains one alteration in cancer gene, the probability of accumulation of a critical mass of additional oncogenic mutations in any given cell clone is high, and cancer manifestation often occurs at a relatively young age.

Figure 2 Main hereditary cancer genes and organs at risk. This figure illustrates major hereditary cancer types observed in females, males, adults of both genders, and children.

Figure 3 Management of hereditary cancer syndromes. PARPi: Poly (ADP-ribose) polymerase inhibitors; TMB: Tumor mutation burden; HIF-2α: Hypoxia inducible factor-2α; VHL: von Hippel-Lindau; mTOR: Mechanistic target of rapamycin; MAPK: Mitogen-activated protein kinase signaling pathway; MEK: Mitogen-activated protein kinase; VEGFR: Vascular endothelial growth factor receptor; SMO: Smoothened; CMMRD: Constitutional mismatch repair deficiency syndrome.