Copy number profiles of paired primary and metastatic colorectal cancers

Futoshi Kawamata; Ann-Marie Patch; Katia Nones; Catherine Bond; Diane McKeone; Sally-Anne Pearson; Shigenori Homma; Cheng Liu; Lochlan Fennell; Troy Dumenil; Gunter Hartel; Nozomi Kobayashi; Hideki Yakoo; Moto Fukai; Hiroshi Nishihara; Toshiya Kamiyama; Matthew E Burge; Christos S Karapetis; Akinobu Taketomi; Barbara Leggett; Nicola Waddell; Vicki Whitehall

doi:10.18632/oncotarget.23277

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Copy number profiles of paired primary and metastatic colorectal cancers

Journal article

Open access

Peer reviewed

Copy number profiles of paired primary and metastatic colorectal cancers

Futoshi Kawamata, Ann-Marie Patch, Katia Nones, Catherine Bond, Diane McKeone, Sally-Anne Pearson, Shigenori Homma, Cheng Liu, Lochlan Fennell, Troy Dumenil, …

Oncotarget, Vol.9(3), pp.3394-3405

2018

DOI: https://doi.org/10.18632/oncotarget.23277

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Abstract

Oncology and Carcinogenesis

Chemotherapy

colorectal cancer

liver metastasis

loss of heterozygosity

copy number alterations

Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC). In this study, we compared the copy number profiles of paired primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. Paired primary and metastatic tumors from 16 patients and their adjacent normal tissue samples were analyzed using single nucleotide polymorphism arrays. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 188 genes known to be somatically altered in CRC and 24 genes that are clinically actionable in CRC. These data were analyzed with respect to the timing of primary and metastatic tissue resection and with exposure to chemotherapy. The genomic differences between the tumor and paired metastases revealed an average copy number discordance of 22.0%. The pairs of tumor samples collected prior to treatment revealed significantly higher copy number differences compared to post-therapy liver metastases (P = 0.014). Loss of heterozygosity acquired in liver metastases was significantly higher in previously treated liver metastasis samples compared to treatment naive liver metastasis samples (P = 0.003). Amplification of the clinically actionable genes ERBB2, FGFR1, PIK3CA or CDK8 was observed in the metastatic tissue of 4 patients but not in the paired primary CRC. These examples highlight the intra-patient genomic discrepancies that can occur between metastases and the primary tumors from which they arose. We propose that precision medicine strategies may therefore identify different actionable targets in metastatic tissue, compared to primary tumors, due to substantial genomic differences.

Details

Title: Copy number profiles of paired primary and metastatic colorectal cancers
Authors: Futoshi Kawamata (Author) - Queensland Medical Institute of Research
Ann-Marie Patch (Author) - Queensland Medical Institute of Research
Katia Nones (Author) - Queensland Medical Institute of Research
Catherine Bond (Author) - Queensland Medical Institute of Research
Diane McKeone (Author) - Queensland Medical Institute of Research
Sally-Anne Pearson (Author) - Queensland Medical Institute of Research
Shigenori Homma (Author) - Hokkaido University Graduate School of Medicine, Japan
Cheng Liu (Author) - Queensland Medical Institute of Research
Lochlan Fennell (Author) - Queensland Medical Institute of Research
Troy Dumenil (Author) - Queensland Medical Institute of Research
Gunter Hartel (Author) - Queensland Medical Institute of Research
Nozomi Kobayashi (Author) - Hokkaido University Graduate School of Medicine, Japan
Hideki Yakoo (Author) - Hokkaido University Graduate School of Medicine, Japan
Moto Fukai (Author) - Hokkaido University Graduate School of Medicine, Japan
Hiroshi Nishihara (Author) - Hokkaido University Graduate School of Medicine, Japan
Toshiya Kamiyama (Author) - Hokkaido University Graduate School of Medicine, Japan
Matthew E Burge (Author) - Royal Brisbane and Women's Hospital
Christos S Karapetis (Author) - Flinders University
Akinobu Taketomi (Author) - Hokkaido University Graduate School of Medicine, Japan
Barbara Leggett (Author) - Queensland Medical Institute of Research
Nicola Waddell (Author) - Queensland Medical Institute of Research
Vicki Whitehall (Author) - Queensland Medical Institute of Research
Publication details: Oncotarget, Vol.9(3), pp.3394-3405
Publisher: Impact Journals LLC
Date published: 2018
DOI: 10.18632/oncotarget.23277
ISSN: 1949-2553
Copyright note: Copyright © Kawamata et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source. are credited.
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451188202621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Cell Biology; Oncology

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