Analyse von KRAS-Mutation, Kopienanzahl und numerischen Veränderungen der Chromosomen 4,10 und 12 beim kolorektalen Karzinom
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. Colorectal adenocarcinomas (n=54) 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. 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). There was no association between the ploidy status and the sequence profiles of KRAS or KRAS mutation status. 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.
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