Copy number profiles of paired primary and metastatic colorectal cancers

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

Research output: Contribution to journalArticle

2 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 - 2018 Jan 1
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Neoplasm Metastasis
Liver
Neoplasms
Precision Medicine
Loss of Heterozygosity
Neoplasm Genes
Genes
Single Nucleotide Polymorphism
Cause of Death
Therapeutics
Genome
Drug Therapy

Keywords

  • Chemotherapy
  • Colorectal cancer
  • Copy number alterations
  • Liver metastasis
  • Loss of heterozygosity

ASJC Scopus subject areas

  • Oncology

Cite this

Kawamata, F., Patch, A. M., Nones, K., Bond, C., McKeone, D., Pearson, S. A., ... Whitehall, V. (2018). Copy number profiles of paired primary and metastatic colorectal cancers. Oncotarget, 9(3), 3394-3405. https://doi.org/10.18632/oncotarget.23277

Copy number profiles of paired primary and metastatic colorectal cancers. / Kawamata, Futoshi; Patch, Ann Marie; Nones, Katia; Bond, Catherine; McKeone, Diane; Pearson, Sally Ann; Homma, Shigenori; Liu, Cheng; Fennell, Lochlan; Dumenil, Troy; Hartel, Gunter; Kobayasi, Nozomi; Yokoo, Hideki; Fukai, Moto; Nishihara, Hiroshi; Kamiyama, Toshiya; Burge, Matthew E.; Karapetis, Christos S.; Taketomi, Akinobu; Leggett, Barbara; Waddell, Nicola; Whitehall, Vicki.

In: Oncotarget, Vol. 9, No. 3, 01.01.2018, p. 3394-3405.

Research output: Contribution to journalArticle

Kawamata, F, Patch, AM, Nones, K, Bond, C, McKeone, D, Pearson, SA, Homma, S, Liu, C, Fennell, L, Dumenil, T, Hartel, G, Kobayasi, N, Yokoo, H, Fukai, M, Nishihara, H, Kamiyama, T, Burge, ME, Karapetis, CS, Taketomi, A, Leggett, B, Waddell, N & Whitehall, V 2018, 'Copy number profiles of paired primary and metastatic colorectal cancers', Oncotarget, vol. 9, no. 3, pp. 3394-3405. https://doi.org/10.18632/oncotarget.23277
Kawamata F, Patch AM, Nones K, Bond C, McKeone D, Pearson SA et al. Copy number profiles of paired primary and metastatic colorectal cancers. Oncotarget. 2018 Jan 1;9(3):3394-3405. https://doi.org/10.18632/oncotarget.23277
Kawamata, Futoshi ; Patch, Ann Marie ; Nones, Katia ; Bond, Catherine ; McKeone, Diane ; Pearson, Sally Ann ; Homma, Shigenori ; Liu, Cheng ; Fennell, Lochlan ; Dumenil, Troy ; Hartel, Gunter ; Kobayasi, Nozomi ; Yokoo, Hideki ; Fukai, Moto ; Nishihara, Hiroshi ; Kamiyama, Toshiya ; Burge, Matthew E. ; Karapetis, Christos S. ; Taketomi, Akinobu ; Leggett, Barbara ; Waddell, Nicola ; Whitehall, Vicki. / Copy number profiles of paired primary and metastatic colorectal cancers. In: Oncotarget. 2018 ; Vol. 9, No. 3. pp. 3394-3405.
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AB - 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.

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