近日，韩国成均馆大学医学院Yeon Hee Park及其小组研制了1364例乳腺癌的全基因组图谱。该项研究成果发表在2025年12月3日出版的《自然》上。

为了全面表征其基因组景观和基因组特征的临床意义，研究团队分析了1364例临床注释乳腺癌的全基因组序列，其中大多数病例的转录组数据可用。他们的研究扩大了致癌改变的范围，并确定了新的驱动基因、复发性基因突变、结构变异和拷贝数改变。拷贝数改变的时间分析表明，基因组不稳定性在肿瘤诊断前几十年就出现了，这为肿瘤发生的早期开始提供了见解。模式驱动的基因组特征，包括突变特征、同源重组缺陷、肿瘤突变负担和肿瘤异质性评分，与临床结果相关，突出了它们作为临床评估治疗（如CDK4/6和HER2抑制剂）以及辅助和新辅助化疗的预测性生物标志物的潜在效用。这些发现突出了大规模、临床注释的全基因组测序在促进他们对基因组改变如何影响患者预后的理解方面的力量。

据了解，乳腺癌仍然是一个重大的全球健康挑战。

附：英文原文

Title: Whole-genome landscapes of 1,364 breast cancers

Author: Kim, Ryul, Yu, Jonghan, Lim, Joonoh, Oh, Brian Baek-Lok, Nam, Seok Jin, Kim, Seok Won, Lee, Jeong Eon, Chae, Byung Joo, Kim, Ji-Yeon, Park, Ga Eun, Kang, Bong Joo, Paik, Pill Sun, Bae, Soo Yeon, Yoon, Chang Ik, Lee, Young Joo, Kim, Dooreh, Shin, Kabsoo, Lee, Ji Eun, Kang, Jun, Lee, Ahwon, Connolly-Strong, Erin, Lee, Sangmoon, Lee, Bo Rahm, Lee, Yuna, Yi, Ki Jong, Kwon, Young Oh, Chun, In Hwan, Park, Junggil, Kim, Jihye, Choi, Chahyun, Shin, Jong Yeon, Lee, Hyungjung, Kim, Minji, Park, Hansol, Jeong, Ilecheon, Yi, Boram, Lee, Won-Chul, Lee, Jeong Seok, Park, Woo Chan, Kim, Sung Hun, Choi, Yoon-La, Lee, Jeongmin, Ju, Young Seok, Park, Yeon Hee

Issue&Volume: 2025-12-03

Abstract: Breast cancer remains a major global health challenge1. Here, to comprehensively characterize its genomic landscape and the clinical significance of genomic characteristics, we analysed whole-genome sequences from 1,364 clinically annotated breast cancers, with transcriptome data available for most cases. Our study expands the repertoire of oncogenic alterations and identifies novel driver genes, recurrent gene fusions, structural variants and copy number alterations. Timing analyses on copy number alterations suggest that genomic instability emerges decades before tumour diagnosis, and offer insights into early initiation of tumorigenesis. Pattern-driven genomic features, including mutational signatures2, homologous recombination deficiency3, tumour mutational burden and tumour heterogeneity scores4, were associated with clinical outcomes, highlighting their potential utility as predictive biomarkers for clinical evaluation of treatments such as CDK4/6 and HER2 inhibitors, as well as adjuvant and neoadjuvant chemotherapy. These findings highlight the power of large-scale, clinically annotated whole-genome sequencing in advancing our understanding of how genomic alterations shape patient outcomes.

DOI: 10.1038/s41586-025-09812-3

Source: https://www.nature.com/articles/s41586-025-09812-3