title: KRAS and aneusomy of chromosomes 4, 10 and 12 in colorectal carcinomas.
abstract: OBJECTIVE
  KRAS mutation status has predictive significance in EGFR-antibody treatment of colorectal adenocarcinoma. The aim of the study was the evaluation of KRAS mutation status in correlation to KRAS copy numbers and ploidy status.
  
  
  METHODS
  Colorectal adenocarcinomas (n=52) were assembled into a TMA and analyzed by FISH. Probes for centromeres 4 and 10 were applied as surrogate markers for the ploidy status. In addition, a dual color FISH probe set for the centromere of chromosome 12 and the KRAS gene was applied to the TMA to analyze numerical alterations and KRAS gene copy numbers. Further we analyzed DNA sequence profiles of KRAS codons 12 and 13 to assess the allele status of the mutation within the tumor samples.
  
  
  RESULTS
  KRAS mutation was confirmed in 24 cases, while 28 cases showed a wild-type KRAS status. The majority of cases showed diploid FISH signals for chromosomes 4 and 10. Near triploid FISH signals were observed in only 2 cases, 12 cases were hypodiploid, and 8 cases were hyperdiploid. In 6 cases, trisomy 12 could be ascertained. In total, aneuploidy could be detected in 28 cases, including cases with trisomy 12 and hyposomy 10. Tumors with aneuploid chromosomal content had a worse prognosis compared to euploid tumors, however, without reaching statistical significance (p=0.231). Hypodiploid carcinomas carried the worst prognosis. Specifically, monosomy 10 was significantly associated with reduced survival (p=0.039). Increased FISH signals of KRAS did not correlate significantly with relapse (p=0.916).
  
  
  CONCLUSIONS
  FISH analysis can be used as a surrogate marker for the ploidy status. Loss of chromosome 10 may serve as a potential adverse prognostic marker being indicative for tumor progression.
authors.affiliation: Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Ziegelmühlenweg 1, 07743 Jena, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Beyer
authors.affiliation: Department of General and Visceral and Vascular Surgery, Jena University Hospital, Friedrich-Schiller-University, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Annelore
authors.initials: A
authors.lastname: Altendorf-Hofmann
authors.affiliation: Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Ziegelmühlenweg 1, 07743 Jena, Germany.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of General and Visceral Surgery, St. Georg Klinikum, Mühlhäuser Straße 94-95, 99817 Eisenach, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bickel
authors.affiliation: Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, Ziegelmühlenweg 1, 07743 Jena, Germany. Electronic address: iver.petersen@med.uni-jena.de.
authors.forename: Iver
authors.initials: I
authors.lastname: Petersen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10; D002881:Chromosomes, Human, Pair 12; D002894:Chromosomes, Human, Pair 4; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010641:Phenotype; D011003:Ploidies; D011237:Predictive Value of Tests; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Aneusomy; Chromosomal instability; Colon cancer; Ploidy; RAS