TY - JOUR
T1 - Genomic profiling reveals heterogeneous populations of ductal carcinoma in situ of the breast
AU - Nagasawa, Satoi
AU - Kuze, Yuta
AU - Maeda, Ichiro
AU - Kojima, Yasuyuki
AU - Motoyoshi, Ai
AU - Onishi, Tatsuya
AU - Iwatani, Tsuguo
AU - Yokoe, Takamichi
AU - Koike, Junki
AU - Chosokabe, Motohiro
AU - Kubota, Manabu
AU - Seino, Hibiki
AU - Suzuki, Ayako
AU - Seki, Masahide
AU - Tsuchihara, Katsuya
AU - Inoue, Eisuke
AU - Tsugawa, Koichiro
AU - Ohta, Tomohiko
AU - Suzuki, Yutaka
N1 - Funding Information:
We thank all the patients who participated in this study. We thank K. Imamura, K. Abe, Y. Ishikawa, M. Konbu, E. Kobayashi, E. Ishikawa, and T. Horiuchi for their technical assistance. This research was supported by grants from the JSPS Fujita Memorial Fund for Medical Research and the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI Grants) Number 16H06279 (Platform for Advanced Genome Science).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s42003-021-01959-9
DO - 10.1038/s42003-021-01959-9
M3 - Article
C2 - 33795819
AN - SCOPUS:85103808066
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 438
ER -