POLD1 and brain neoplasm: In addition to POLE/POLD1 variants, these include CDH1 aberrations causing hereditary diffuse gastric cancer syndrome that may also increase the risk of brain tumors of neuroepithelial and epithelial origin [7], and variants in the MMR genes MLH1, MSH2, MSH6, or PMS2 causing constitutional MMR deficiency or hereditary non-polyposis colorectal cancer (or Lynch) syndrome when mutated in a biallelic or heterozygous fashion that are associated with an increased risk of colorectal and brain tumors [38].