POLE and melanoma: The primary gene panel for a syndrome with melanoma and colon cancer includes the melanoma genetic panel and genes that have at least a twofold increase in colon cancer risk including APC, BMPR1A, CDH1, EPCAM, GREM1, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53. Genes that have a strong clinical association also include AXIN2, CHEK2, POLD1, and POLE. The additional preliminary evidence (or research) panel could include ATM, BLM, BUB1B, ENG, FLCN, GALNT12, and MLH3 (Fig. 2).