title: Losses of chromosome 5q and 14q are associated with favorable clinical outcome of patients with gastric cancer.
abstract: OBJECTIVE
  To improve the clinical outcome of patients with gastric cancer, intensified combination strategies are currently in clinical development, including combinations of more extensive surgery, (neo)adjuvant chemotherapy, and radiotherapy. The present study used DNA copy number profiling to identify subgroups of patients with different clinical outcomes. We hypothesize that, by identification of subgroups, individual treatment strategies can be selected to improve clinical outcome and to reduce unnecessary treatment toxicity for patients with gastric cancer.
  
  
  METHODS
  DNA from 206 gastric cancer patients was isolated and analyzed by genomewide array comparative genomic hybridization. DNA copy number profiles were correlated with lymph node status and patient survival. In addition, heat shock protein 90 (HSP90) expression was analyzed and correlated with survival in 230 gastric cancer patients.
  
  
  RESULTS
  Frequent (>20%) DNA copy number gains and losses were observed on several chromosomal regions. Losses on 5q11.2-q31.3 and 14q32.11-q32.33 (14% of patients) were correlated with good clinical outcome in univariate and multivariate analyses, with a median disease-free survival interval of 9.2 years. In addition, loss of expression of HSP90, located on chromosome 14q32.2, was correlated with better patient survival.
  
  
  CONCLUSIONS
  Genomewide DNA copy number profiling allowed the identification of a subgroup of gastric cancer patients, marked by losses on chromosomes 5q11.2-q31.3 and 14q32.11-q32.33 or low HSP90 protein expression, with an excellent clinical outcome after surgery alone. We hypothesize that this subgroup of patients most likely will not benefit from (neo)adjuvant systemic treatment and/or radiotherapy, whereas anti-HSP90 therapy may have clinical potential in patients with HSP90-expressing gastric cancer, pending validation in an independent dataset.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tineke E
authors.initials: TE
authors.lastname: Buffart
authors.forename: Beatriz
authors.initials: B
authors.lastname: Carvalho
authors.forename: Nicole C T
authors.initials: NC
authors.lastname: van Grieken
authors.forename: Wessel N
authors.initials: WN
authors.lastname: van Wieringen
authors.forename: Marianne
authors.initials: M
authors.lastname: Tijssen
authors.forename: Elma Meershoek-Klein
authors.initials: EM
authors.lastname: Kranenbarg
authors.forename: Henk M W
authors.initials: HM
authors.lastname: Verheul
authors.forename: Heike I
authors.initials: HI
authors.lastname: Grabsch
authors.forename: Bauke
authors.initials: B
authors.lastname: Ylstra
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002883:Chromosomes, Human, Pair 14; D002895:Chromosomes, Human, Pair 5; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D018841:HSP90 Heat-Shock Proteins