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Background <p>Although mutations in TP53 and BRCA1/2 are central to the biology of breast and ovarian cancers, their prognostic roles remain debated, with little attention to tissue-specific differences. Understanding whether the same mutation carries opposite survival implications across cancer types could reshape biomarker interpretation.</p> Methods <p>We interrogated TCGA cohorts of breast cancer (<i>n</i> = 967) and ovarian cancer (OV; <i>n</i> = 571), defining mutation status by non-synonymous variants. Overall survival was assessed using Kaplan–Meier and multivariable Cox regression models, adjusted for clinical covariates. Complete-case subsets were analyzed for robustness.</p> Results <p>In breast cancer, BRCA2 mutations conferred a strikingly adverse prognosis (HR = 3.91; 95% CI, 1.10–13.9; <i>p</i> = 0.034), while BRCA1 and TP53 showed no clear effects. By contrast, in OV, BRCA2 mutations were linked to markedly improved survival (HR = 0.18; 95% CI, 0.04–0.82; <i>p</i> = 0.018). BRCA1 showed a trend toward benefit, whereas TP53 mutations, though nearly ubiquitous, were not prognostic.</p> Conclusions <p>This work uncovers a paradoxical, tissue-specific divergence in the prognostic value of BRCA2 mutations: detrimental in breast cancer yet favorable in OV. Such opposing effects have not been systematically highlighted before and emphasize the need for cancer-type–tailored biomarker strategies. These results are hypothesis-generating but highlight the translational importance of context in precision oncology.</p>

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Tissue specific prognostic impact of TP53 and BRCA1 and BRCA2 mutations in breast and ovarian cancers using TCGA data

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Parvin Pourmasoumi

摘要

Background

Although mutations in TP53 and BRCA1/2 are central to the biology of breast and ovarian cancers, their prognostic roles remain debated, with little attention to tissue-specific differences. Understanding whether the same mutation carries opposite survival implications across cancer types could reshape biomarker interpretation.

Methods

We interrogated TCGA cohorts of breast cancer (n = 967) and ovarian cancer (OV; n = 571), defining mutation status by non-synonymous variants. Overall survival was assessed using Kaplan–Meier and multivariable Cox regression models, adjusted for clinical covariates. Complete-case subsets were analyzed for robustness.

Results

In breast cancer, BRCA2 mutations conferred a strikingly adverse prognosis (HR = 3.91; 95% CI, 1.10–13.9; p = 0.034), while BRCA1 and TP53 showed no clear effects. By contrast, in OV, BRCA2 mutations were linked to markedly improved survival (HR = 0.18; 95% CI, 0.04–0.82; p = 0.018). BRCA1 showed a trend toward benefit, whereas TP53 mutations, though nearly ubiquitous, were not prognostic.

Conclusions

This work uncovers a paradoxical, tissue-specific divergence in the prognostic value of BRCA2 mutations: detrimental in breast cancer yet favorable in OV. Such opposing effects have not been systematically highlighted before and emphasize the need for cancer-type–tailored biomarker strategies. These results are hypothesis-generating but highlight the translational importance of context in precision oncology.