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Breast Cancer Research and Treatment

Erschienen in:

05.05.2024 | Original Laboratory Investigation

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

verfasst von: Ruoxi Hong, Boyang Cao, Dongshao Chen, Wei Wu, Tian Luo, Dian Lv, Weimin Zhang, Shusen Wang, Kang Shao

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2024

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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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Titel: Multi-omics portrait of ductal carcinoma in situ in young women
verfasst von: Ruoxi Hong
Boyang Cao
Dongshao Chen
Wei Wu
Tian Luo
Dian Lv
Weimin Zhang
Shusen Wang
Kang Shao
Publikationsdatum: 05.05.2024
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2024
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-024-07254-5

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