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Multi-omics portrait of ductal carcinoma in situ in young women

  • Original Laboratory Investigation
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Young patients with breast ductal carcinoma in situ (DCIS) often face a poorer prognosis. The genomic intricacies in young-onset DCIS, however, remain underexplored.

Methods

To address this gap, we undertook a comprehensive study encompassing exome, transcriptome, and vmethylome analyses. Our investigation included 20 DCIS samples (including 15 young-onset DCIS) and paired samples of normal breast tissue and blood.

Results

Through RNA sequencing, we identified two distinct DCIS subgroups: “immune hot” and “immune cold”. The “immune hot” subgroup was characterized by increased infiltration of lymphocytes and macrophages, elevated expression of PDCD1 and CTLA4, and reduced GATA3 expression. This group also exhibited active immunerelated transcriptional regulators. Mutational analysis revealed alterations in TP53 (38%), GATA3 (25%), and TTN (19%), with two cases showing mutations in APC, ERBB2, and SMARCC1. Common genomic alterations, irrespective of immune status, included gains in copy numbers at 1q, 8q, 17q, and 20q, and losses at 11q, 17p, and 22q. Signature analysis highlighted the predominance of signatures 2 and 1, with “immune cold” samples showing a significant presence of signature 8. Our methylome study on 13 DCIS samples identified 328 hyperdifferentially methylated regions (DMRs) and 521 hypo-DMRs, with “immune cold” cases generally showing lower levels of methylation.

Conclusion

In summary, the molecular characteristics of young-onset DCIS share similarities with invasive breast cancer (IBC), potentially indicating a poor prognosis. Understanding these characteristics, especially the immune microenvironment of DCIS, could be pivotal in identifying new therapeutic targets and preventive strategies for breast cancer.

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Data availability

The datasets generated during and/or analyzed during the current study can be available from the corresponding author on reasonable request, following ethics committee approval and a data transfer agreement. Please contact the corresponding author, S.W. (email address: wangshs@sysucc.org.cn) to request access to the data.

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Acknowledgements

This research was supported by the Guangdong Provincial Key Laboratory of Human Disease Genomics (2020B1212070028). This work was supported by the China National GeneBank (CNGB).

Funding

This work was supported by the National Natural Science Foundation of China (82372590, 82303007), Natural Science Foundation of Guangdong Province (2023A1515030092, 2020A1515010105), Guangdong Basic and Applied Basic Research Foundation (2022A1515111202), Fostering Program for NSFC Young Applicants (Tulip Talent Training Program) of Sun Yat-sen University Cancer Center (2023yfd10).

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Author notes

  1. Ruoxi Hong, Boyang Cao and Dongshao Chen these authors have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Department of Medical Oncology, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P.R. China

    Ruoxi Hong, Dongshao Chen, Wei Wu & Shusen Wang

  2. HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, BGI Research, Hangzhou, 310030, China

    Boyang Cao, Tian Luo, Dian Lv & Kang Shao

  3. Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI-Research, Shenzhen, 518083, China

    Boyang Cao, Tian Luo, Dian Lv & Kang Shao

  4. Institute of Intelligent Medical Research (IIMR), BGI Genomics, Shenzhen, 518083, China

    Weimin Zhang

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  1. Ruoxi Hong
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Contributions

Concept and design: WZ, SW, KS. Acquisition, analysis, or interpretation of data: RH, BC, DC. Drafting of the manuscript: DC. Critical revision of the manuscript for important intellectual content: RH. Statistical analysis: BC. Administrative, technical, or material support: WW, TL, DL. Supervision: WZ, SW, KS.

Corresponding authors

Correspondence to Weimin Zhang, Shusen Wang or Kang Shao.

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The authors have no relevant financial or non-financial interests to disclose.

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The study was approved by the ethical committee of Sun Yat-sen University Cancer Center and waived the requirement for informed consent due to the retrospective nature of this study.

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Hong, R., Cao, B., Chen, D. et al. Multi-omics portrait of ductal carcinoma in situ in young women. Breast Cancer Res Treat (2024). https://doi.org/10.1007/s10549-024-07254-5

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