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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, A ; Verwaal, V J LU ; de Groot, K A ; Morreau, H and van Velthuysen, M-L F , et al. (2011) In British Journal of Cancer 105(2). p.281-287
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, n=39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n=46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM,... (More)

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, n=39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n=46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n=48).

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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publishing date
type
Contribution to journal
publication status
published
keywords
Adult, Aged, Aged, 80 and over, Carcinoma/genetics, Chromosome Aberrations, Cohort Studies, Colorectal Neoplasms/genetics, DNA Mutational Analysis, Disease Progression, Female, Follow-Up Studies, Genome-Wide Association Study, Humans, Liver Neoplasms/genetics, Male, Middle Aged, Mutation/physiology
in
British Journal of Cancer
volume
105
issue
2
pages
281 - 287
publisher
Nature Publishing Group
external identifiers
  • scopus:79960225815
  • pmid:21673680
ISSN
1532-1827
DOI
10.1038/bjc.2011.184
language
English
LU publication?
no
id
788f75ff-7e78-4939-9269-67c9448f6f7f
date added to LUP
2022-04-05 11:16:27
date last changed
2024-01-09 12:39:41
@article{788f75ff-7e78-4939-9269-67c9448f6f7f,
  abstract     = {{<p>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.</p><p>METHODS: Formalin-fixed paraffin-embedded material from primary colorectal tumours of three different groups were investigated: patients with CRC without metastases (M0, n=39), patients who were treated with hyperthermal intraperitoneal chemotherapy for CRC metastases confined to the peritoneum (PM, n=46) and those who had isolated hepatic perfusion for CRC metastases confined to the liver (LM, n=48).</p><p>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.</p><p>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.</p>}},
  author       = {{Bruin, S C and He, Y and Mikolajewska-Hanclich, I and Liefers, G-J and Klijn, C and Vincent, A and Verwaal, V J and de Groot, K A and Morreau, H and van Velthuysen, M-L F and Tollenaar, R A E M and van 't Veer, L J}},
  issn         = {{1532-1827}},
  keywords     = {{Adult; Aged; Aged, 80 and over; Carcinoma/genetics; Chromosome Aberrations; Cohort Studies; Colorectal Neoplasms/genetics; DNA Mutational Analysis; Disease Progression; Female; Follow-Up Studies; Genome-Wide Association Study; Humans; Liver Neoplasms/genetics; Male; Middle Aged; Mutation/physiology}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{281--287}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Molecular alterations associated with liver metastases development in colorectal cancer patients}},
  url          = {{http://dx.doi.org/10.1038/bjc.2011.184}},
  doi          = {{10.1038/bjc.2011.184}},
  volume       = {{105}},
  year         = {{2011}},
}