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转移性乳腺癌基因组图谱问世
作者:小柯机器人 发布时间:2019/10/2 20:43:06

荷兰鹿特丹大学医学院John W. M. Martens课题组近日取得一项新成果。他们利用转移性乳腺癌的基因组图谱揭示了突变和特征频率的变化。2019年9月30日,《自然—遗传学》在线发表了这项成果。

研究人员对442例转移性乳腺癌患者的前瞻性组织活检进行全基因组测序后发现,与原发性乳腺癌相比,肿瘤的突变负担增加了一倍,突变特征的相对贡献发生了变化,六个已知驱动基因的突变频率在转移性乳腺癌中增加。

研究人员还观察到与药物治疗的显著关联。在用氟尿嘧啶、紫杉烷类、铂类和/或艾瑞布林进行治疗的患者中,突变特征17的作用显著富集。在这项研究中确定的从头突变特征I与铂类化学疗法的治疗显著相关。研究人员确定了与临床相关的肿瘤亚群,其表现出同源重组缺陷(13%),高肿瘤突变负担(11%)或与对FDA批准药物敏感相关的特异性改变(24%)。

这项研究提供了对转移性乳腺癌生物学的见解,并确定了可用于将来改善患者治疗的临床可用基因组特征。

附:英文原文

Title: The genomic landscape of metastatic breast cancer highlights changes in mutation and signature frequencies

Author: Lindsay Angus, Marcel Smid, Saskia M. Wilting, Job van Riet, Arne Van Hoeck, Luan Nguyen, Serena Nik-Zainal, Tessa G. Steenbruggen, Vivianne C. G. Tjan-Heijnen, Mariette Labots, Johanna M. G. H. van Riel, Haiko J. Bloemendal, Neeltje Steeghs, Martijn P. Lolkema, Emile E. Voest, Harmen J. G. van de Werken, Agnes Jager, Edwin Cuppen, Stefan Sleijfer, John W. M. Martens

Issue&Volume: 2019-09-30

Abstract: 

The whole-genome sequencing of prospectively collected tissue biopsies from 442 patients with metastatic breast cancer reveals that, compared to primary breast cancer, tumor mutational burden doubles, the relative contributions of mutational signatures shift and the mutation frequency of six known driver genes increases in metastatic breast cancer. Significant associations with pretreatment are also observed. The contribution of mutational signature 17 is significantly enriched in patients pretreated with fluorouracil, taxanes, platinum and/or eribulin, whereas the de novo mutational signature I identified in this study is significantly associated with pretreatment containing platinum-based chemotherapy. Clinically relevant subgroups of tumors are identified, exhibiting either homologous recombination deficiency (13%), high tumor mutational burden (11%) or specific alterations (24%) linked to sensitivity to FDA-approved drugs. This study provides insights into the biology of metastatic breast cancer and identifies clinically useful genomic features for the future improvement of patient management.

DOI: 10.1038/s41588-019-0507-7

Source:https://www.nature.com/articles/s41588-019-0507-7

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex