With the wide application of next generation sequencing, the co-mutation genes in different tumors were detected, such as, the co-mutation of TP53, STK11, CDKN2A and KMT2C in lung cancer; the co-mutation of TP53, KRAS, ARID1A, PIK3CA, CDKN2A, SMARCA4, PBRM1, STK11, APC and RB1 in cancer of unknown primary; the co-mutation of ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53 in breast cancer; and the co-mutation of KRAS, GNAS, AKT1, APC, PIK3CA, RB1, STK11 and TP53 in low-grade mucinous neoplasms [93–96]. Here, PIK3CA is linked to cancer.