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Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women

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Abstract

Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at <55 years) African American (AA) and Caucasian American (CA) women originally enrolled in a larger population-based study. We compared the average frequency of CNAs across the whole genome for each breast tumor subtype and found that estrogen receptor (ER)-negative tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.02) compared to ER-positive tumors. Triple-negative (TN) tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.003) than non-TN tumors. No significant difference in CNA frequency was observed between HER2-positive and -negative tumors. We also identified previously unreported recurrent CNAs (frequency >40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women.

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Acknowledgments

The authors would like to thank Stephanie Stafford for assistance with data management and analysis, the leadership and staff of the FHCRC DNA Array Facility and Jeri Glogovac for flow sorting of tumor samples. The study was supported by funding from NCI RO1 CA64292, P. I. William Eley; NCI R01 CA098415, P. I. Peggy Porter.

Conflict of interest

All authors report no conflict of interest associated with this study.

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Author notes

  1. Lenora W. M. Loo

    Present address: Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI, USA

Authors and Affiliations

  1. Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N C1-015, Seattle, WA, 98109, USA

    Lenora W. M. Loo, Erin M. Flynn & Peggy L. Porter

  2. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Yinghui Wang, Li Hsu & Peggy L. Porter

  3. Department of Pathology, University of Washington, Seattle, WA, USA

    Peggy L. Porter

  4. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Mary Jo Lund & Jonathan M. Liff

  5. Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA

    Erin J. Aiello Bowles & Diana S. M. Buist

  6. Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Elaine W. Flagg

  7. National Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Ralph J. Coates

  8. Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Mary Jo Lund & J. William Eley

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  1. Lenora W. M. Loo
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  2. Yinghui Wang
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  10. J. William Eley
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  11. Li Hsu
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Correspondence to Peggy L. Porter.

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Loo, L.W.M., Wang, Y., Flynn, E.M. et al. Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women. Breast Cancer Res Treat 127, 297–308 (2011). https://doi.org/10.1007/s10549-010-1297-x

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