RB1 gene mutations and their association with Endometrial Cancer

Abstract Retinoblastoma gene (RB1) mutation has been reported in lung cancer, retinoblastoma and cervical cancer etc. Here, we elucidate the involvement of RB1 mutations and their regulation in endometrial cancer. Analysis of mutation data of 547 endometrial cancer samples revealed that 12% of samples harboured RB1 mutations. However, 26% of the patients aged between 30 and 50 years harboured RB1 mutations, compared to only 10% in the older age group. Further, in silico interaction studies and structural analysis of these novel RB1 mutations and E2F revealed possible physiological relevance. We found 14,117 genes were significantly mutated, and 5,770 genes were differentially expressed in RB1-altered patients. Pathway analysis showed a significant correlation between RB1 mutations and estrogen receptor mutations. Different cancer-related pathways were also altered in RB1-mutated conditions. More importantly, a positive link between RB1 mutations and HPV infection pathways was observed, indicating HPV infections might induce RB1 mutations in endometrial cancer, which could be prevented by early vaccination. Our findings suggest RB1 mutations as a potential contributor to endometrial cancer in younger women, highlighting the importance of viral co-factors in risk assessments, advocating HPV vaccination in individuals with RB1 mutations.