Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast

Satoi Nagasawa, Yuta Kuze, Ichiro Maeda, Yasuyuki Kojima, Ai Motoyoshi, Tatsuya Onishi, Tsuguo Iwatani, Takamichi Yokoe, Junki Koike, Motohiro Chosokabe, Manabu Kubota, Hibiki Seino, Ayako Suzuki, Masahide Seki, Katsuya Tsuchihara, Eisuke Inoue, Koichiro Tsugawa, Tomohiko Ohta, Yutaka Suzuki

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


In a substantial number of patients, ductal carcinoma in situ (DCIS) of the breast will never progress to invasive ductal carcinoma, and these patients are often overtreated under the current clinical criteria. Although various candidate markers are available, relevant markers for delineating risk categories have not yet been established. In this study, we analyzed the clinical characteristics of 431 patients with DCIS and performed whole-exome sequencing analysis in a 21-patient discovery cohort and targeted deep sequencing analysis in a 72-patient validation cohort. We determined that age <45 years, HER2 amplification, and GATA3 mutation are possible indicators of relapse. PIK3CA mutation negativity and PgR negativity were also suggested to be risk factors. Spatial transcriptome analysis further revealed that GATA3 dysfunction upregulates epithelial-to-mesenchymal transition and angiogenesis, followed by PgR downregulation. These results reveal the existence of heterogeneous cell populations in DCIS and provide predictive markers for classifying DCIS and optimizing treatment.

Original languageEnglish
Article number438
JournalCommunications biology
Issue number1
Publication statusPublished - 2021 Dec
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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