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Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization

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Abstract

Although a simple linear progression model for breast cancer has already been proposed, its validity still remains controversial. Especially, the genetic and molecular features of breast cancer at different stages during the development and progression, as well as their relationship, have rarely been studied under the same experimental conditions simultaneously. According to these limitations in this research area, the current study applied comparative genomic hybridization technique to investigate genomic changes in 15 cases of breast atypical ductal hyperplasia (ADH), 15 cases of ductal carcinomas in situ (DCIS), and 15 cases of invasive ductal carcinomas (IDC) and the relationship among the genetic changes. Thirty commonly altered regions that were identified included known (gains of 1q,8q, 17q,20q,Xq and losses of 8p,13q,16q,17p,22q) and several uncharacterized (gains of 2q,5p, 10p,12q,16p,18q, etc. and losses of 11p13-pter,11q,14q,Xp, etc). The overall frequency of copy number losses was higher in IDC than that in DCIS (P = 0.013). ADH showed more frequent gain of 17q than that in IDC (P = 0.007), and IDC exhibited a higher frequency for the loss of 22q than that in ADH (P = 0.018). On one hand, several common genomic changes shared by ADH, DCIS, and IDC make a linear relationship for these three lesions possible. On the other hand, the heterogeneity has also showed clonal diversification and different pathways of breast cancer progression. The regions of chromosomal copy number alterations may bring new insights into the strategy for tumor progression blocking and the discovery of new potential targets for breast cancer treatment.

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Acknowledgements

The authors gratefully acknowledge Chinese National Human Genome Center for the completion of the project. This research project was supported by a grant from the National Natural Science Foundation of China (No: 30471967).

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Authors and Affiliations

  1. Breast Cancer Research Key Laboratory of National (Education Ministry), Cancer Institute and Hospital, Tianjin Medical University, Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin, 300060, China

    Yuxia Gao, Yun Niu & Li Wei

  2. Molecular Cytogenetics Laboratory, Chinese National Human Genome Center, #3-707 North Yong Chang Road, BDA, Beijing, 100176, China

    Xiaowei Wang

  3. Laboratory of Kidney Physician Department, General Hospital, Tianjin Medical University, #154 An Shan Road, He Ping District, Tianjin, 300052, China

    Li Wei

  4. Department of Biochemistry, the University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong Special Administrative Region (SAR), China

    Song Lu

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  1. Yuxia Gao
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  2. Yun Niu
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  3. Xiaowei Wang
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  4. Li Wei
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  5. Song Lu
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Correspondence to Yun Niu.

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Gao, Y., Niu, Y., Wang, X. et al. Genetic changes at specific stages of breast cancer progression detected by comparative genomic hybridization. J Mol Med 87, 145–152 (2009). https://doi.org/10.1007/s00109-008-0408-1

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  • DOI: https://doi.org/10.1007/s00109-008-0408-1

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