Abstract
Background: Breast cancer is the second most common malignancy in women and considered as a severe health burden. PEG3 mutations have been observed in several cancers. However, the associations of PEG3 mutation with tumor mutation burden (TMB) and prognosis in breast cancer have not been investigated. Methods: In our study, the somatic mutation data of 986 breast cancer patients from The Cancer Genome Atlas (TCGA) were analyzed. Results: It showed that PEG3 had a relatively high mutation rate (2%). After calculated the TMB in PEG3 mutant and PEG3 wild-type groups, we found the TMB value was significantly higher in PEG3 mutant samples than that in PEG3 wild-type samples (P = 5.6e-07), which was independent of the confounding factors including age, stage, mutations of BRCA1, BRCA2 and POLE (odd ratio, 0.45; 95% CI, 0.20–0.98; P=0.044). Survival analysis revealed that PEG3 mutant samples had inferior survival outcome compared with the PEG3 wild-type samples after adjusted for the confounding factors above (hazard ratio, 0.27; 95% CI: 0.12–0.57; P<0.001). Conclusion: These results illustrated that PEG3 mutation was associated with high TMB and inferior prognosis, suggesting PEG3 mutation might play a guiding role in prognosis prediction and immunotherapy selection in breast cancer.
Highlights
Breast cancer is recognized as the second most common malignancy with the feature of distinct metastasis, which involves in liver, lung, lymph nodes and bone marrow [1,2]
We calculated the mutation rates of the top 40 mutated genes (Figure 1A), imprinted genes (PEG3, UBE3A, GRB10, PEG10, SNRPN, NDN) and genes that might affect the mutation rates of the genome (BRCA1, BRCA2, POLE, MLH3) (Figure 1B) respectively, and the result revealed that PEG3 and BRCA2 presented relatively high mutation rates in the breast cancer samples
Mutations of BRCA2, BRCA1, MLH3 and POLE is associated with high mutation frequencies in breast cancer patients
Summary
Breast cancer is recognized as the second most common malignancy with the feature of distinct metastasis, which involves in liver, lung, lymph nodes and bone marrow [1,2]. Almost one in eight women is diagnosed with breast cancer in America, and the incidence rate increases with age [3,4]. The prognosis of breast cancer patients is not optimistic. More investigations on the underlying molecular mechanism may be significant for timely surveillance as well as improved prognosis of breast cancer. Breast cancer is the second most common malignancy in women and considered as a severe health burden. The associations of PEG3 mutation with tumor mutation burden (TMB) and prognosis in breast cancer have not been investigated. Results: It showed that PEG3 had a relatively high mutation rate (2%). Conclusion: These results illustrated that PEG3 mutation was associated with high TMB and inferior prognosis, suggesting PEG3 mutation might play a guiding role in prognosis prediction and immunotherapy selection in breast cancer
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