The mutational landscape of the adult healthy parous and nulliparous human breast.
The mutational landscape of the adult healthy parous and nulliparous human breast.
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DOI：
10.1038/s41467-023-40608-z
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发表时间：
2023-09-06
影响因子：
16.6
通讯作者：
Stebbing, Justin
中科院分区：
文献类型：
--
作者：
Cereser, Biancastella;Yiu, Angela;Tabassum, Neha;Del Bel Belluz, Lisa;Zagorac, Sladjana;Ancheta, Kenneth Russell Zapanta;Zhong, Rongrong;Miere, Cristian;Jeffries-Jones, Alicia Rose;Moderau, Nina;Werner, Benjamin;Stebbing, Justin
体细胞突变在健康人体组织中的积累已被广泛表征，但健康乳腺的突变景观仍然知之甚少。我们对全基因组测序的分析表明，与其他健康器官一致，生殖期的健康乳房随着年龄的增长而积累突变，上皮细胞中的积累率为15.24 ± 5个突变/年。上皮和间质区室都含有乳腺特异性驱动基因的突变，表明随后的阳性选择。产次和年龄相关的差异在乳腺上皮中是明显的，这部分解释了不同生育年龄妇女之间观察到的乳腺癌风险差异。胎次与年龄依赖性增加的突变上皮细胞的克隆大小，这表明，年龄较大的第一次母亲有更高的概率在上皮细胞中积累致癌事件相比，年轻的母亲或未经产的妇女。总之，我们描述了生殖期健康女性人类乳腺的参考基因组，并提供了奇偶性如何影响乳腺基因组景观的证据。虽然人们已经对许多组织的自然体细胞突变进行了研究，但人类乳腺组织尚未得到很好的研究。在这里，作者描述了人类乳腺组织中的体细胞突变，发现了年龄和产次的影响。
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. While many tissues have been investigated for natural somatic mutations, human breast tissue has not been well studied. Here, the authors characterize somatic mutations in human breast tissue, finding effects of age and parity.
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影响因子：
12.3
作者：
Blokzijl F;Janssen R;van Boxtel R;Cuppen E
通讯作者：
Cuppen E
影响因子：
7.7
作者：
Haricharan, Svasti;Dong, Jie;Li, Yi
通讯作者：
Li, Yi
影响因子：
7
作者：
Eberle, Michael A.;Fritzilas, Epameinondas;Bentley, David R.
通讯作者：
Bentley, David R.
DOI：
10.1016/s1470-2045(21)00183-2
发表时间：
2021-06
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Amant F;Lefrère H;Borges VF;Cardonick E;Lambertini M;Loibl S;Peccatori F;Partridge A;Schedin P
通讯作者：
Schedin P
影响因子：
3.8
作者：
Casey, M. C.;Prakash, A.;Brown, J. A.
通讯作者：
Brown, J. A.