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Proteomics Clin Appl. 2018 Sep;12(5):e1700125. doi: 10.1002/prca.201700125. Epub 2018 Mar 30.

Integrated Multi-Omic Analyses Support Distinguishing Secretory Carcinoma of the Breast from Basal-Like Triple-Negative Breast Cancer.

Author information

1
Department of Pathology, Bucheon St. Mary's Hospital, College of Medicine, Catholic University of Korea, Bucheon, Gyeonggi-do, South Korea.
2
Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
3
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
4
Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
5
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
6
Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.

Abstract

PURPOSE:

Secretory carcinoma (SC) of the breast is defined as an indolent tumor but is still categorized into a basal-like triple-negative breast cancer (BL-TNBC) subgroup that generally shows aggressive behavior according to the current classification. Despite the unique clinical behavior of SC, molecular characteristics that reflect biological behaviors of SC remain largely unknown.

EXPERIMENTAL DESIGN:

A combinatorial approach of whole-exome sequencing and mass spectrometry-based in-depth quantitative proteomics to determine the entire molecular landscape of SC using three SC formalin-fixed paraffin-embedded (FFPE) tissues is employed.

RESULTS:

Exome sequencing and proteomic analysis of SC identified 419 unique somatic mutations and 721 differentially expressed proteins as compared with triple-negative breast cancer (TNBC), respectively. Several pathways related to cancer metabolism were significantly upregulated in the SC group. Comparative analyses with multiple datasets revealed that SC shares genomic mutations and biological pathways more closely related to hormone receptor-positive breast cancer than BL-TNBC.

CONCLUSION AND CLINICAL RELEVANCE:

These multi-omic analyses provide evidence that SC harbors substantially different molecular genomic and proteomic landscapes compared with BL-TNBC. These results provide an entire spectrum of in-depth molecular landscapes to support the hypothesis that SC is distinct from BL-TNBC.

KEYWORDS:

Bioinformatics; Cancer genomics; Cancer proteomics; Secretory carcinoma of the breast; Triple-negative breast cancer

PMID:
29476606
DOI:
10.1002/prca.201700125
[Indexed for MEDLINE]

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