Exome sequencing of synchronously resected primary colorectal tumours and colorectal liver metastases to inform oncosurgical management

P. A. Sutton, Puthen V. Jithesh, R. P. Jones, J. P. Evans, D. Vimalachandran, H. Z. Malik, B. K. Park, C. E. Goldring, D. H. Palmer, N. R. Kitteringham

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Next generation sequencing technology has facilitated mapping of the colorectal cancer genotype and furthered our understanding of metastogenesis. The aim of this study was to investigate for conserved and different mutations in the exomes of synchronously resected primary colorectal tumour and liver metastases. This information could potentially be utilised to guide the treatment of advanced disease with the help of biological information from the primary tumour. Methods We performed exome sequencing of synchronously resected primary colorectal cancer and colorectal liver metastases as well as normal colonic mucosa and liver parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a depth of 50X using the Ion Proton platform. Raw data was mapped to the reference genome prior to variant calling, annotation and downstream analysis. Results Exome sequencing identified 585 non-synonymous missense single nucleotide variants (SNVs), of which 215 (36.8%) were unique to the primary tumour, 226 (38.6%) unique to the metastasis and 81 (13.8%) present in patient matched pairs. SNVs identified in the ErbB pathway appear to be concordant between primary and metastatic tumours. Conclusion Only 13.8% of the metastatic exome can be predicted by the genotype of the primary tumour. We have demonstrated concordance of a number of SNVs in the ErbB pathway, which may inform selection of therapeutic agents in advanced colorectal cancer.

Original languageEnglish
Pages (from-to)115-121
Number of pages7
JournalEuropean Journal of Surgical Oncology
Volume44
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Exome
Colorectal Neoplasms
Neoplasm Metastasis
Nucleotides
Liver
Neoplasms
Genotype
Adjuvant Chemotherapy
Liver Neoplasms
Protons
Mucous Membrane
Genome
Ions
Technology
Mutation
Therapeutics

Keywords

  • Colorectal cancer
  • Exome
  • Next generation sequencing
  • Stage IV
  • Synchronous resection

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Exome sequencing of synchronously resected primary colorectal tumours and colorectal liver metastases to inform oncosurgical management. / Sutton, P. A.; Jithesh, Puthen V.; Jones, R. P.; Evans, J. P.; Vimalachandran, D.; Malik, H. Z.; Park, B. K.; Goldring, C. E.; Palmer, D. H.; Kitteringham, N. R.

In: European Journal of Surgical Oncology, Vol. 44, No. 1, 01.01.2018, p. 115-121.

Research output: Contribution to journalArticle

Sutton, PA, Jithesh, PV, Jones, RP, Evans, JP, Vimalachandran, D, Malik, HZ, Park, BK, Goldring, CE, Palmer, DH & Kitteringham, NR 2018, 'Exome sequencing of synchronously resected primary colorectal tumours and colorectal liver metastases to inform oncosurgical management', European Journal of Surgical Oncology, vol. 44, no. 1, pp. 115-121. https://doi.org/10.1016/j.ejso.2017.10.211
Sutton, P. A. ; Jithesh, Puthen V. ; Jones, R. P. ; Evans, J. P. ; Vimalachandran, D. ; Malik, H. Z. ; Park, B. K. ; Goldring, C. E. ; Palmer, D. H. ; Kitteringham, N. R. / Exome sequencing of synchronously resected primary colorectal tumours and colorectal liver metastases to inform oncosurgical management. In: European Journal of Surgical Oncology. 2018 ; Vol. 44, No. 1. pp. 115-121.
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abstract = "Background Next generation sequencing technology has facilitated mapping of the colorectal cancer genotype and furthered our understanding of metastogenesis. The aim of this study was to investigate for conserved and different mutations in the exomes of synchronously resected primary colorectal tumour and liver metastases. This information could potentially be utilised to guide the treatment of advanced disease with the help of biological information from the primary tumour. Methods We performed exome sequencing of synchronously resected primary colorectal cancer and colorectal liver metastases as well as normal colonic mucosa and liver parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a depth of 50X using the Ion Proton platform. Raw data was mapped to the reference genome prior to variant calling, annotation and downstream analysis. Results Exome sequencing identified 585 non-synonymous missense single nucleotide variants (SNVs), of which 215 (36.8{\%}) were unique to the primary tumour, 226 (38.6{\%}) unique to the metastasis and 81 (13.8{\%}) present in patient matched pairs. SNVs identified in the ErbB pathway appear to be concordant between primary and metastatic tumours. Conclusion Only 13.8{\%} of the metastatic exome can be predicted by the genotype of the primary tumour. We have demonstrated concordance of a number of SNVs in the ErbB pathway, which may inform selection of therapeutic agents in advanced colorectal cancer.",
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AU - Evans, J. P.

AU - Vimalachandran, D.

AU - Malik, H. Z.

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N2 - Background Next generation sequencing technology has facilitated mapping of the colorectal cancer genotype and furthered our understanding of metastogenesis. The aim of this study was to investigate for conserved and different mutations in the exomes of synchronously resected primary colorectal tumour and liver metastases. This information could potentially be utilised to guide the treatment of advanced disease with the help of biological information from the primary tumour. Methods We performed exome sequencing of synchronously resected primary colorectal cancer and colorectal liver metastases as well as normal colonic mucosa and liver parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a depth of 50X using the Ion Proton platform. Raw data was mapped to the reference genome prior to variant calling, annotation and downstream analysis. Results Exome sequencing identified 585 non-synonymous missense single nucleotide variants (SNVs), of which 215 (36.8%) were unique to the primary tumour, 226 (38.6%) unique to the metastasis and 81 (13.8%) present in patient matched pairs. SNVs identified in the ErbB pathway appear to be concordant between primary and metastatic tumours. Conclusion Only 13.8% of the metastatic exome can be predicted by the genotype of the primary tumour. We have demonstrated concordance of a number of SNVs in the ErbB pathway, which may inform selection of therapeutic agents in advanced colorectal cancer.

AB - Background Next generation sequencing technology has facilitated mapping of the colorectal cancer genotype and furthered our understanding of metastogenesis. The aim of this study was to investigate for conserved and different mutations in the exomes of synchronously resected primary colorectal tumour and liver metastases. This information could potentially be utilised to guide the treatment of advanced disease with the help of biological information from the primary tumour. Methods We performed exome sequencing of synchronously resected primary colorectal cancer and colorectal liver metastases as well as normal colonic mucosa and liver parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a depth of 50X using the Ion Proton platform. Raw data was mapped to the reference genome prior to variant calling, annotation and downstream analysis. Results Exome sequencing identified 585 non-synonymous missense single nucleotide variants (SNVs), of which 215 (36.8%) were unique to the primary tumour, 226 (38.6%) unique to the metastasis and 81 (13.8%) present in patient matched pairs. SNVs identified in the ErbB pathway appear to be concordant between primary and metastatic tumours. Conclusion Only 13.8% of the metastatic exome can be predicted by the genotype of the primary tumour. We have demonstrated concordance of a number of SNVs in the ErbB pathway, which may inform selection of therapeutic agents in advanced colorectal cancer.

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