Somatic alterations in YO-CRC differ from those observed in older adults: BRAF V600E mutations occur in <5% of cases; KRAS mutations are found in 40–50%, primarily in exfon 2; microsatellite instability (MSI) is present in 15–20%; POLE or POLD1 mutations are reported in 3–5%; and HER2 amplification is observed in 2–3% [11,14,15,16]. The gene discussed is POLE; the disease is colorectal carcinoma.