Whole-genome landscapes of 1,364 breast cancers
Breast cancer remains a major global health challenge<sup>1</sup>. 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 signatures<sup>2</sup>, homologous recombination deficiency<sup>3</sup>, tumour mutational burden and tumour heterogeneity scores<sup>4</sup>, 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.
Authors
- H K Lee
- Dooreh Kim (ORCID: https://orcid.org/0000-0003-1758-4439)
- Byung Joo Chae (ORCID: https://orcid.org/0000-0003-1564-0978)
- Young Oh Kwon
- Joonoh Lim (ORCID: https://orcid.org/0000-0002-2836-8259)
- Yuna Lee (ORCID: https://orcid.org/0000-0003-3700-0824)
- Ilecheon Jeong
- Kabsoo Shin (ORCID: https://orcid.org/0000-0002-6709-0894)
- Pill Sun Paik (ORCID: https://orcid.org/0000-0001-8480-5567)
- Bong Joo Kang (ORCID: https://orcid.org/0000-0002-5991-6035)
- Young Seok Ju (ORCID: https://orcid.org/0000-0002-5514-4189)
- Baek‐Lok Oh (ORCID: https://orcid.org/0000-0001-6007-5176)
- Seok Jin Nam (ORCID: https://orcid.org/0000-0003-1072-8954)
- Chang Ik Yoon (ORCID: https://orcid.org/0000-0002-1795-5781)
- Ryul Kim (ORCID: https://orcid.org/0000-0002-8754-9180)
- Erin Connolly-Strong
- Ga Eun Park (ORCID: https://orcid.org/0000-0002-2479-6950)
- Jonghan Yu (ORCID: https://orcid.org/0000-0001-9546-100X)
- Woo Chan Park (ORCID: https://orcid.org/0000-0002-1265-1981)
- Ji‐Yeon Kim (ORCID: https://orcid.org/0000-0002-4223-1929)
- Ah-Won Lee
- Jun Kang (ORCID: https://orcid.org/0000-0002-7967-0917)
- Soo Youn Bae (ORCID: https://orcid.org/0000-0003-0551-7618)
- Min‐Ji Kim (ORCID: https://orcid.org/0000-0002-4525-7542)
- Jihye Kim (ORCID: https://orcid.org/0000-0002-8969-9369)
- Sung Hoon Kim (ORCID: https://orcid.org/0000-0002-1024-1153)
- Young Joo Lee (ORCID: https://orcid.org/0000-0001-5352-8093)
- Jeongmin Lee (ORCID: https://orcid.org/0000-0002-4266-7984)
- Won‐Chul Lee (ORCID: https://orcid.org/0000-0001-8052-2420)
- Sangmoon Lee (ORCID: https://orcid.org/0000-0002-7723-5946)
- Yeon Hee Park (ORCID: https://orcid.org/0000-0003-4156-9212)
- Hansol Park (ORCID: https://orcid.org/0000-0002-2851-4404)
- Jeong Eon Lee (ORCID: https://orcid.org/0000-0003-0037-2456)
- Seok Won Kim (ORCID: https://orcid.org/0000-0002-1910-0242)
- Yoon-La Choi
- In Hwan Chun
- Jung-Gil Park
- Boram Yi
- Ki Jong Yi
- Jeong Seok Lee
- Bo Rahm Lee
- Chahyun Choi
- Jong Yeon Shin
- Ji Eun Lee
Institutions
- Korea Advanced Institute of Science and Technology (KR)
- Madras Institute of Development Studies (IN)
- Samsung Medical Center (KR)
- The Catholic University of Korea Bucheon St. Mary's Hospital (KR)
- The Catholic University of Korea Seoul St. Mary's Hospital (KR)
- Sungkyunkwan University (KR)
- Catholic University of Korea (KR)
Publication Details
- Journal
- Nature
- Published
- 2025-12-03
- DOI
- https://doi.org/10.1038/s41586-025-09812-3
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00