title: Losses at chromosome 4q are associated with poor survival in operable ductal pancreatic adenocarcinoma.
abstract: Here we tested the prognostic impact of genomic alterations in operable localized pancreatic ductal adenocarcinoma (PDAC). Fifty-two formalin-fixed and paraffin-embedded primary PDAC were laser micro-dissected and were investigated by comparative genomic hybridization after whole genome amplification using an adapter-linker PCR. Chromosomal gains and losses were correlated to clinico-pathological parameters and clinical follow-up data. The most frequent aberration was loss on chromosome 17p (65%) while the most frequent gains were detected at 2q (41%) and 8q (41%), respectively. The concomitant occurrence of losses at 9p and 17p was found to be statistically significant. Higher rates of chromosomal losses were associated with a more advanced primary tumor stage and losses at 9p and 18q were significantly associated with presence of lymphatic metastasis (chi-square: p = 0.03, p = 0.05, respectively). Deletions on chromosome 4 were of prognostic significance for overall survival and tumor recurrence (Cox-multivariate analysis: p = 0.026 and p = 0.021, respectively). In conclusion our data suggest the common alterations at chromosome 8q, 9p, 17p and 18q as well as the prognostic relevant deletions on chromosome 4q as relevant for PDAC progression. Our comprehensive data from 52 PDAC should provide a basis for future studies with a higher resolution to discover the relevant genes located within the chromosomal aberrations identified.
authors.affiliation: Klinik und Poliklinik für Allgemein-, Visceral- und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Luebke
authors.forename: M
authors.initials: M
authors.lastname: Baudis
authors.forename: H
authors.initials: H
authors.lastname: Matthaei
authors.forename: Y K
authors.initials: YK
authors.lastname: Vashist
authors.forename: P E
authors.initials: PE
authors.lastname: Verde
authors.forename: S B
authors.initials: SB
authors.lastname: Hosch
authors.forename: A
authors.initials: A
authors.lastname: Erbersdobler
authors.forename: C A
authors.initials: CA
authors.lastname: Klein
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: W T
authors.initials: WT
authors.lastname: Knoefel
authors.forename: N H
authors.initials: NH
authors.lastname: Stoecklein
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002894:Chromosomes, Human, Pair 4; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis