In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 4_Supplement ( 2018-02-15), p. P2-06-01-P2-06-01
Abstract:
Malignant phyllodes tumor (MPT) which belong to the fibroepithelial neoplasm spectrum is a rare type of breast malignancy, and currently there is no effective targeted approach available for MPT. In this study, we tried to identify key genomic alterations and biologic pathways in MPT by whole exome and RNA sequencing of nine MPT tissues. Whole exome sequencing revealed somatic alterations in EGFR, MED12, PIK3CA, PIK3R1, PDGFRA, PDGFRB, PTEN, and TP53. Transcriptome sequencing showed dysregulation of ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling in MPTs when compared to normal breast or invasive breast cancer tissues. Based on the transcriptome profiles, the MPTs were classified into two subtypes; fibrous subtype with upregulation of stromal genes such as collagens and epithelial subtype with upregulation of E-cadherin and Claudins. The molecular classification of fibrous and epithelial subtypes was validated in 28 paraffin-embedded MPT tissues. The fibrous subtype showed higher mitotic index and increased risk for recurrence when compared to the epithelial subtype. We established a patient-derived xenograft model from one fibrous subtype MPT which harbored somatic mutation in PIK3R1 and PDGFRB. In that model, targeted treatment against PIK3CA/mTOR and PDGFR pathways effectively suppressed the tumor growth in vivo. Our data provide insights on the biologic understanding of MPT and suggest a clinically relevant molecular classification. Furthermore, we show that developing effective targeted approaches in MPT can be possible with genomic profiles and patient-derived xenograft models. The clinical efficacy of targeting PDGFR and PIK3CA/mTOR pathways in MPT should be tested in future clinical trials. Citation Format: Moon H-G, Yun J, Hong BS, Lee E, Lee H-B, Han W, Kim J-I, Noh D-Y, Heo W, Hur S, Kang W, Lee C. Molecular characterization of human malignant phyllodes tumors reveals potential targeted approaches [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-06-01.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.SABCS17-P2-06-01
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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