Heterogeneity of genomic profile in patients with HER2-positive breast cancer

in Endocrine-Related Cancer
Authors:
Bo Chen Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Guochun Zhang Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Guangnan Wei Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Yulei Wang Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
School of Medicine, South China University of Technology, Guangzhou, Guangdong, China

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Liping Guo Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China

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Jiali Lin Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China

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Kai Li Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Hsiaopei Mok Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Li Cao Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Chongyang Ren Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Lingzhu Wen Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Minghan Jia Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Cheukfai Li Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Ting Hou Burning Rock Biotech, Guangzhou, Guangdong, China

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Han Han-Zhang Burning Rock Biotech, Guangzhou, Guangdong, China

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Jing Liu Burning Rock Biotech, Guangzhou, Guangdong, China

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Charles M Balch Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

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Ning Liao Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China

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Correspondence should be addressed to N Liao: syliaoning@scut.edu.cn

*(B Chen, G Zhang and G Wei contributed equally to this work)

DOI:
https://doi.org/10.1530/ERC-19-0414
Volume/Issue:
Volume 27: Issue 3
Article Type:
Research Article
Page Range:
153–162
Online Publication Date:
Mar 2020
Copyright:
© 2020 Society for Endocrinology 2020
Restricted access
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HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR− HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

Supplementary Materials

    • Supplementary TableS1. The patients’ clinical characteristics
    • Supplementary Figure S1. Compared GDPH and the TCGA in KEGG pathways (HR+/HER2+ patients).
    • Supplementary Figure S2. Compared GDPH and the METABRIC in KEGG pathways (HR+/HER2+ patients).

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
10
Received Date:
22 Nov 2019
Accepted Date:
24 Dec 2019
Print Publication Date:
01 Mar 2020
Online Publication Date:
Mar 2020
Keywords:
HER2-positive breast cancer; Chinese breast cancer; hormone receptor; mutation landscape; ERBB family

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