日本京都大学Seishi Ogawa课题组揭示乳腺癌及相关克隆的演化史。相关论文于2023年7月26日在线发表于国际学术期刊《自然》。
研究人员通过对癌症和非癌症病变的多个微切片样本进行系统发育分析，展示了携带der(1;16)的乳腺癌的独特演化史，der(1;16)是一种常见的驱动基因改变，在大约20%的乳腺癌中发现。早期演化事件的大致时间是根据正常上皮细胞的突变率估算的。在der(1;16)(+)癌症中，衍生染色体是在青春期早期至青春期晚期获得的，随后在患者30多岁时出现一个共同祖先，癌症和非癌症克隆都是从这个祖先演化而来。
在接下来的几年中，这些克隆取代了原有的乳腺上皮，到癌症确诊时，这些克隆占据了绝经前乳腺组织中的大片区域。从非癌症祖先演化出多个独立癌症创始者的现象很常见，这也是造成肿瘤内异质性的原因之一。驱动事件的数量与组织学无关，这表明局部微环境和/或表观遗传驱动事件起了作用。在另一例由AKT1基因突变演化而来的病例中也观察到了类似的演化模式。综上所述，这些研究结果为乳腺癌的演化过程提供了新的视角。
据介绍，最近的研究表明，在表面正常的组织中，携带常见癌症突变的克隆会频繁演化，这与癌症的发展有关。然而，在正常组织中的一个或多个克隆最终演变为癌症之前，还需要按照什么样的顺序发生哪些额外的驱动事件，人们对此还缺乏了解。
附：英文原文
Title: Evolutionary histories of breast cancer and related clones
Author: Nishimura, Tomomi, Kakiuchi, Nobuyuki, Yoshida, Kenichi, Sakurai, Takaki, Kataoka, Tatsuki R., Kondoh, Eiji, Chigusa, Yoshitsugu, Kawai, Masahiko, Sawada, Morio, Inoue, Takuya, Takeuchi, Yasuhide, Maeda, Hirona, Baba, Satoko, Shiozawa, Yusuke, Saiki, Ryunosuke, Nakagawa, Masahiro M., Nannya, Yasuhito, Ochi, Yotaro, Hirano, Tomonori, Nakagawa, Tomoe, Inagaki-Kawata, Yukiko, Aoki, Kosuke, Hirata, Masahiro, Nanki, Kosaku, Matano, Mami, Saito, Megumu, Suzuki, Eiji, Takada, Masahiro, Kawashima, Masahiro, Kawaguchi, Kosuke, Chiba, Kenichi, Shiraishi, Yuichi, Takita, Junko, Miyano, Satoru, Mandai, Masaki, Sato, Toshiro, Takeuchi, Kengo, Haga, Hironori, Toi, Masakazu, Ogawa, Seishi
Issue&Volume: 2023-07-26
Abstract: Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1,2,3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.
DOI: 10.1038/s41586-023-06333-9
Source: https://www.nature.com/articles/s41586-023-06333-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
