Identification of a characteristic copy number alteration profile by high-resolution single nucleotide polymorphism arrays associated with metastatic sporadic colorectal cancer

Authors

  • María González-González BS,

    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
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  • Celia Fontanillo PhD,

    1. Bioinformatics and Functional Genomics Unit, Institute of Molecular Biology and Cellular Oncology/Spanish National Research Council, University of Salamanca, Salamanca, Spain
    2. Celgene Institute for Translational Research Europe (CITRE), Seville, Spain
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  • María M. Abad MD, PhD,

    1. Department of Pathology, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • María L. Gutiérrez BS,

    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
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  • Ines Mota BS,

    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
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  • Oscar Bengoechea MD, PhD,

    1. Department of Pathology, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Ángel Santos-Briz MD, PhD,

    1. Department of Pathology, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Oscar Blanco MD, PhD,

    1. Department of Pathology, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Emilio Fonseca MD, PhD,

    1. Service of Medical Oncology, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Juana Ciudad PhD,

    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
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  • Manuel Fuentes PhD,

    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
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  • Javier De Las Rivas PhD,

    1. Bioinformatics and Functional Genomics Unit, Institute of Molecular Biology and Cellular Oncology/Spanish National Research Council, University of Salamanca, Salamanca, Spain
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  • José A. Alcazar MD, PhD,

    1. Department of General and Digestive Surgery, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Jacinto García MD, PhD,

    1. Department of General and Digestive Surgery, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Luís Muñoz-Bellvis MD, PhD,

    1. Department of General and Digestive Surgery, University Hospital of Salamanca-Salamanca Institute of Biomedical Research, Salamanca, Spain
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  • Alberto Orfao MD, PhD,

    Corresponding author
    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
    • Corresponding authors: Alberto Orfao, MD, PhD, or José María Sayagués, PhD, Centro de Investigación del Cancer, Paseo de la Universidad de Coimbra S/N, 37007 Salamanca, Spain; Fax: (011) 34-923-294795; orfao@usal.es

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  • José M. Sayagués PhD

    1. General Cytometry Service-Nucleus, Department of Medicine and Cancer Research Center, Institute of Molecular Biology and Cellular Oncology of the University of Salamanca and Salamanca Institute of Biomedical Research, University of Salamanca, Salamanca, Spain
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  • The last 2 authors contributed equally to this work.

Abstract

BACKGROUND

Metastatic dissemination is the most frequent cause of death in patients with sporadic colorectal cancer (sCRC). It is believed that the metastatic process is related at least in part to a specific background of genetic alterations accumulated in cells from primary tumors, and the ability to detect such alterations is critical for the identification of patients with sCRC who are at risk of developing metastases.

METHODS

The authors used high-resolution, 500-K single nucleotide polymorphism arrays to identify copy number alteration profiles present at diagnosis in primary tumors from patients with metastatic (n = 23) versus nonmetastatic (n = 26) sCRC.

RESULTS

The results revealed a characteristic pattern of copy number alterations in metastatic sCRC tumors that involved losses of 23 regions at chromosomes 1p, 17p, and 18q, together with gains of 35 regions at chromosomes 7 and 13q.

CONCLUSIONS

In line with expectations, the copy number profile investigated involved multiple genes that were associated previously with sCRC (ie, SMAD2) and/or the metastatic process (ie, podocalyxin-like [PODXL]), and it also was associated with a poorer outcome. Cancer 2014;120:1948–1959. © 2014 American Cancer Society.

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