title: Molecular alterations associated with liver metastases development in colorectal cancer patients.
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, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Division of Experimental Therapy, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Bruin
authors.forename: Y
authors.initials: Y
authors.lastname: He
authors.forename: I
authors.initials: I
authors.lastname: Mikolajewska-Hanclich
authors.forename: G-J
authors.initials: GJ
authors.lastname: Liefers
authors.forename: C
authors.initials: C
authors.lastname: Klijn
authors.forename: A
authors.initials: A
authors.lastname: Vincent
authors.forename: V J
authors.initials: VJ
authors.lastname: Verwaal
authors.forename: K A
authors.initials: KA
authors.lastname: de Groot
authors.forename: H
authors.initials: H
authors.lastname: Morreau
authors.forename: M-L F
authors.initials: ML
authors.lastname: van Velthuysen
authors.forename: R A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: L J
authors.initials: LJ
authors.lastname: van 't Veer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002869:Chromosome Aberrations; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology