Molecular alterations associated with liver metastases development in colorectal cancer patients

S. C. Bruin, Y. He, I. Mikolajewska-Hanclich, G. J. Liefers, C. Klijn, Andrew Vincent, V. J. Verwaal, K. A. De Groot, H. Morreau, M. L.F. Van Velthuysen, R. A.E.M. Tollenaar, L. J. Van't Veer

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background:Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.Methods:Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n48).Results:All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations.Conclusion:The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.

LanguageEnglish
Pages281-287
Number of pages7
JournalBritish Journal of Cancer
Volume105
Issue number2
DOIs
Publication statusPublished - 12 Jul 2011

Keywords

  • KRAS
  • PI(3)K signalling pathway
  • PIK3CA
  • chromosome 20q
  • colorectal cancer
  • liver metastases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bruin, S. C., He, Y., Mikolajewska-Hanclich, I., Liefers, G. J., Klijn, C., Vincent, A., ... Van't Veer, L. J. (2011). Molecular alterations associated with liver metastases development in colorectal cancer patients. British Journal of Cancer, 105(2), 281-287. https://doi.org/10.1038/bjc.2011.184
Bruin, S. C. ; He, Y. ; Mikolajewska-Hanclich, I. ; Liefers, G. J. ; Klijn, C. ; Vincent, Andrew ; Verwaal, V. J. ; De Groot, K. A. ; Morreau, H. ; Van Velthuysen, M. L.F. ; Tollenaar, R. A.E.M. ; Van't Veer, L. J. / Molecular alterations associated with liver metastases development in colorectal cancer patients. In: British Journal of Cancer. 2011 ; Vol. 105, No. 2. pp. 281-287.
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abstract = "Background:Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.Methods:Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n48).Results:All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations.Conclusion:The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.",
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Bruin, SC, He, Y, Mikolajewska-Hanclich, I, Liefers, GJ, Klijn, C, Vincent, A, Verwaal, VJ, De Groot, KA, Morreau, H, Van Velthuysen, MLF, Tollenaar, RAEM & Van't Veer, LJ 2011, 'Molecular alterations associated with liver metastases development in colorectal cancer patients', British Journal of Cancer, vol. 105, no. 2, pp. 281-287. https://doi.org/10.1038/bjc.2011.184

Molecular alterations associated with liver metastases development in colorectal cancer patients. / Bruin, S. C.; He, Y.; Mikolajewska-Hanclich, I.; Liefers, G. J.; Klijn, C.; Vincent, Andrew; Verwaal, V. J.; De Groot, K. A.; Morreau, H.; Van Velthuysen, M. L.F.; Tollenaar, R. A.E.M.; Van't Veer, L. J.

In: British Journal of Cancer, Vol. 105, No. 2, 12.07.2011, p. 281-287.

Research output: Contribution to journalArticle

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T1 - Molecular alterations associated with liver metastases development in colorectal cancer patients

AU - Bruin, S. C.

AU - He, Y.

AU - Mikolajewska-Hanclich, I.

AU - Liefers, G. J.

AU - Klijn, C.

AU - Vincent, Andrew

AU - Verwaal, V. J.

AU - De Groot, K. A.

AU - Morreau, H.

AU - Van Velthuysen, M. L.F.

AU - Tollenaar, R. A.E.M.

AU - Van't Veer, L. J.

PY - 2011/7/12

Y1 - 2011/7/12

N2 - Background:Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.Methods:Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n48).Results:All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations.Conclusion:The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.

AB - Background:Understanding the molecular biology of colorectal cancer (CRC) provides opportunities for effective personalised patient management. We evaluated whether chromosomal aberrations, mutations in the PI(3)K signalling pathway and the CpG-island methylator phenotype (CIMP) in primary colorectal tumours can predict liver metastases.Methods:Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n48).Results:All samples were analysed for DNA copy number changes, PIK3CA, KRAS, BRAF mutations, CIMP and microsatellite instability. The primary CRCs of the LM group had significantly higher frequency of amplified chromosome 20q (P=0.003), significantly fewer mutations in the PI(3)K signalling pathway (P=0.003) and fewer CIMP high tumours (P=0.05). There was a strong inverse correlation between 20q and the PI(3)K pathway mutations.Conclusion:The development of CRC liver metastases is associated with amplification of chromosome 20q and not driven by mutations in the PI(3)K signalling pathway.

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KW - PI(3)K signalling pathway

KW - PIK3CA

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