RB1 and cancer: On the other hand, the non-papillary MIBCs are developing from flat dysplasia and carcinoma in situ (CIS) and are characterized by genetic alterations in tumor suppressor genes such as tumor protein p53 (TP53), cyclin dependent kinase inhibitor 2A (CDKN2A), Cyclin D1 (CCND1), cyclin dependent kinase inhibitor 1B (CDKN1B) and RB transcriptional corepressor 1 (RB1) [14].