title: DNA copy number profiles of primary tumors as predictors of response to chemotherapy in advanced colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer (CRC) is biologically a heterogeneous disease, which may affect response to drug therapy. We investigated the correlation of genome-wide DNA copy number profiles of primary tumors with response to systemic chemotherapy in advanced CRC.
  
  
  METHODS
  DNA was isolated from formaldehyde-fixed paraffin-embedded primary tumors of 32 patients with advanced CRC, which were selected based on either a good response (n = 16) or a poor response (n = 16) to first-line combination therapy with capecitabine and irinotecan. High-resolution DNA copy number profiles were obtained by means of 30 K oligonucleotide-based array comparative genomic hybridization (aCGH).
  
  
  RESULTS
  Unsupervised hierarchical cluster analysis of the aCGH data revealed two clusters of 19 and 13 tumors, respectively, and cluster membership showed a significant correlation with response status (P < 0.03). The nonresponders had fewer chromosomal alterations compared with the responders, in particular less losses were found (P < 0.03). Most prominent differences between the two groups were losses of regions 18p11.32-q11.2 (P < 0.02) and 18q12.1-q23 (P < 0.03), which were more frequently observed in responders.
  
  
  CONCLUSIONS
  Differences in DNA copy number profiles of primary CRCs are associated with response to systemic combination chemotherapy with capecitabine and irinotecan. Responders overall had more chromosomal alterations, especially loss of chromosome 18.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Postma
authors.forename: M
authors.initials: M
authors.lastname: Koopman
authors.forename: T E
authors.initials: TE
authors.lastname: Buffart
authors.forename: P P
authors.initials: PP
authors.lastname: Eijk
authors.forename: B
authors.initials: B
authors.lastname: Carvalho
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: B
authors.initials: B
authors.lastname: Ylstra
authors.forename: J H
authors.initials: JH
authors.lastname: van Krieken
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: G A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D018628:Gene Dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin