The adaptive evolution of cancer driver genes

Gu, Langyu; Xia, Canwei; Yang, Shiyu; Yang, Guimei

doi:10.1186/s12864-023-09301-9

Cited by 3 publications

(1 citation statement)

References 72 publications

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“…This discrepancy could be attributed to the fact that many cancer driver genes played adaptive roles in early primate evolution, but lost their significance in the human lineage. Surprisingly, neither BRCA1 nor BRCA2 exhibited signs of positive selection in humans, even though they might have in other primates and in ancestral hominins prior to the gorilla divergence [36].…”

Section: Vestiges Of Positive Selection In Modern Humans Versus Other...mentioning

confidence: 89%

Oncogenic BRCA1,2 Mutations in the Human Lineage—A By-Product of Sexual Selection?

Korneenko,

Pestov

2023

Biomedicines

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In this review, we discuss the long-known problem of tissue-specific carcinogenesis in BRCA1 and BRCA2 mutation carriers: while the genes are expressed ubiquitously, increased cancer risk is observed mostly in the breast and ovaries, and to a much lesser extent, in some other tissues such as the prostate or pancreas. We reevaluate hypotheses on the evolutionary origin of these mutations in humans. Also, we align together the reports that at least some great apes have much lower risks of epithelial cancers in general and breast cancer in particular with the fact that humans have more voluminous breast tissue as compared to their closest extant relatives, particularly chimpanzees and bonobos. We conjecture that this disparity may be a consequence of sexual selection, augmented via selection for enhanced lactation. Further, we argue that there is an organ-specific enigma similar to the Peto paradox: breast cancer risk in humans is only minimally correlated with breast size. These considerations lead to the hypothesis that, along with the evolutionary development of larger breasts in humans, additional changes have played a balancing role in suppressing breast cancer. These yet-to-be-discovered mechanisms, while purely speculative, may be valuable to understanding human breast cancer, though they may not be exclusive to the mammary gland epithelial cells. Combining these themes, we review some anti-carcinogenesis preventive strategies and prospects of new interventions against breast cancer.

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Section: Vestiges Of Positive Selection In Modern Humans Versus Other...mentioning

confidence: 89%

Oncogenic BRCA1,2 Mutations in the Human Lineage—A By-Product of Sexual Selection?

Korneenko,

Pestov

2023

Biomedicines

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The Genomics Evolutionary of Cancer-Associated Pathogens

Velázquez-Márquez,

Núñez-Farfán

2024

Pathogens Associated With the Development of Cancer in Humans

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Exploring the connection between BRCA2 and thyroid cancer

Liu,

Wang

2024

Oncol Transl Med

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Background This study investigated the multifaceted role of BRCA2 (breast cancer 2) in various cancer types, with a specific focus on thyroid carcinoma (THCA). Methods Data sets were obtained from the University of California Santa Cruz database to analyze BRCA2 expression, genetic alterations, and clinical implications. Sample filtering criteria were applied, and immunohistochemistry from the Human Protein Atlas was used to validate protein expression. Correlation analyses were used to explore associations between immune-related genes, and immunological signatures were assessed using various tools. Genetic alterations in BRCA2 were analyzed using cBioPortal, and prognostic analysis involved evaluating gene expression differences at different clinical stages of THCA. Results In patients with THCA, differences in BRCA2 expression were observed at both the mRNA and protein levels when comparing tumor and normal tissues. Correlation studies revealed associations between BRCA2 and immune-related genes, emphasizing its potential role in modulating the tumor microenvironment. Immunological signature analyses indicated distinct frequencies of tumor-infiltrating immune cell subsets in BRCA2 high versus low tumors. Moreover, genetic alterations in BRCA2, particularly the A2738S mutation in exon 18, have been identified in patients with THCA. The prognostic analysis demonstrated a significant correlation between altered BRCA2 levels and improved overall survival in patients with THCA. Additionally, BRCA2 expression was associated with prognostic factors such as stage and N. Conclusions This study provides a holistic exploration of BRCA2 in cancer and highlights its diverse roles in expression, immune modulation, genetic alterations, and clinical prognosis. These findings underscore the potential significance of BRCA2 as a diagnostic and prognostic marker and offer valuable insights for future research and potential clinical applications in cancer management.

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The adaptive evolution of cancer driver genes

Cited by 3 publications

References 72 publications

Oncogenic BRCA1,2 Mutations in the Human Lineage—A By-Product of Sexual Selection?

Oncogenic BRCA1,2 Mutations in the Human Lineage—A By-Product of Sexual Selection?

The Genomics Evolutionary of Cancer-Associated Pathogens

Exploring the connection between BRCA2 and thyroid cancer

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