Here, using long-read whole genome sequencing to analyze CRC tumors from 21 patients, we (1) precisely and reliably detected somatic SVs across the cancer genomes, (2) showed the representative large-scale inversions that altered the expression or structure of key tumor suppressor genes, such as APC and CFTR, in CRC; (3) discovered a novel gene fusion RNF38-RAD51B that could increase the migration, invasion and metastasis ability of CRC cells. Here, RNF38 is linked to cancer.