RNF43 and neoplasm: Frameshift mutations in RNF43 hotspots occurred significantly more frequently in our study case and LS individuals with multiple tumors (p = 0.0001 by Fisher’s Exact Test; Supplementary Table S3); 73.3% (11/15) tumor samples of LS-298, and 60.0% (9/15) of F1001 tumors, versus 10% (2/15) of tumors from control LS with sufficient DNA for testing.