The mutational landscape of the adult healthy parous and nulliparous human breast.

Autor: Cereser B; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK. b.cereser@imperial.ac.uk., Yiu A; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Tabassum N; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Del Bel Belluz L; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Zagorac S; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK.; Molecular Oncology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain., Ancheta KRZ; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK.; Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, UK., Zhong R; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Miere C; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Jeffries-Jones AR; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Moderau N; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK., Werner B; Evolutionary Dynamics Group, Centre for Cancer Genomics and Computational Biology, Barts Cancer Institute, Queen Mary University of London, London, UK., Stebbing J; Cancer Genetics Group, Department of Surgery and Cancer, Imperial College London, London, UK. justin.stebbing@aru.ac.uk.; Department of Life Sciences, Anglia Ruskin University (ARU), Cambridge, UK. justin.stebbing@aru.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 06; Vol. 14 (1), pp. 5136. Date of Electronic Publication: 2023 Sep 06.
DOI: 10.1038/s41467-023-40608-z
Abstrakt: The accumulation of somatic mutations in healthy human tissues has been extensively characterized, but the mutational landscape of the healthy breast is still poorly understood. Our analysis of whole-genome sequencing shows that in line with other healthy organs, the healthy breast during the reproduction years accumulates mutations with age, with the rate of accumulation in the epithelium of 15.24 ± 5 mutations/year. Both epithelial and stromal compartments contain mutations in breast-specific driver genes, indicative of subsequent positive selection. Parity- and age-associated differences are evident in the mammary epithelium, partly explaining the observed difference in breast cancer risk amongst women of different childbearing age. Parity is associated with an age-dependent increase in the clone size of mutated epithelial cells, suggesting that older first-time mothers have a higher probability of accumulating oncogenic events in the epithelium compared to younger mothers or nulliparous women. In conclusion, we describe the reference genome of the healthy female human breast during reproductive years and provide evidence of how parity affects the genomic landscape of the mammary gland.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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