Copy number profiles of paired primary and metastatic colorectal cancers

Futoshi Kawamata, Ann-Marie Patch, Katia Nones, Catherine Bond, Diane McKeone, Sallie-Anne Pearson, Shigenori Homma, Cheng Liu, Lochlan Fennell, Troy Dumenil, Gunter Hartel, Nozomi Kobayasi, Hideki Yokoo, Moto Fukai, Hiroshi Nishihara, Toshiya Kamiyama, Matthew Burge, Christos Karapetis, Akinobu Taketomi, Barbara LeggettNicola Waddell, Vicki Whitehall

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)3394-3405
    Number of pages12
    JournalOncotarget
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - 2017

    Fingerprint Dive into the research topics of 'Copy number profiles of paired primary and metastatic colorectal cancers'. Together they form a unique fingerprint.

  • Cite this

    Kawamata, F., Patch, A-M., Nones, K., Bond, C., McKeone, D., Pearson, S-A., Homma, S., Liu, C., Fennell, L., Dumenil, T., Hartel, G., Kobayasi, N., Yokoo, H., Fukai, M., Nishihara, H., Kamiyama, T., Burge, M., Karapetis, C., Taketomi, A., ... Whitehall, V. (2017). Copy number profiles of paired primary and metastatic colorectal cancers. Oncotarget, 9(3), 3394-3405. https://doi.org/10.18632/oncotarget.23277