METCDS lesions often feature loss of PTPN11 variant heterozygosity (LOH).65,83 In contrast to PTPN11 GOF variants associated with other human neoplasms,66,84–86 LOH of PTPN11 variants drives cartilage tumor development, suggesting that PTPN11 functions as a tumor suppressor in cartilage. This evidence concerns the gene PTPN11 and neoplasm.