title: Alterations in Tumor DNA Are Related to Short Postoperative Survival in Patients Resected for Pancreatic Carcinoma Aimed at Cure.
abstract: Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival.
  
  
  
  DNA was extracted from tumor tissue from 59 PDAC patients, analyzed for KRAS mutations, and hybridized to 180 K CGH + SNP microarrays and 450 K methylation arrays. Analyses were based on postoperative survival where less than 12 months was considered to be short survival and more than 18 months was considered long survival.
  
  
  
  Ninety-three percent of the patients had KRAS mutations in tumor DNA. Great heterogeneity of whole genome DNA sequence alterations were observed among chromosomes within the patient materials. Specific DNA sequence alterations did not directly predict postoperative survival, although short survivors had significantly more and larger DNA amplifications (P < 0.006). Amplifications on chromosome 11 and 21 and deletions on chromosome 2 predicted short postoperative survival (P < 0.03). DNA methylation was not related to survival.
  
  
  
  Highly variable genetic differences among DNA regions in PDAC tumors were demonstrated. Postoperative short survival was related to tumor sequence DNA alterations on chromosome 2, 11, and 21.
authors.affiliation: From the *Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, and †Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; ‡Department of Surgery, and §Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors.forename: Annika Gustafsson
authors.initials: AG
authors.lastname: Asting
authors.forename: David
authors.initials: D
authors.lastname: Ljungman
authors.forename: Helena
authors.initials: H
authors.lastname: Carén
authors.forename: Zilvinas
authors.initials: Z
authors.lastname: Dambrauskas
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Iresjö
authors.forename: Anders
authors.initials: A
authors.lastname: Hyltander
authors.forename: Peter
authors.initials: P
authors.lastname: Naredi
authors.forename: Kent
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D011184:Postoperative Period; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)