Kolorektal kanser ve öncü lezyonlarında KRAS ve BRAF mutasyon analizleri yoluyla tanısal yaklaşım ve hedefe yönelik tedavi seçimi
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Date
2011
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Biyoteknoloji Enstitüsü
Abstract
Colorectal carcinoma is one of the leading causes of cancer death in the Western world and its incidence has been increasing in our country. In order to have a successful therapeutic approach to colorectal carcinoma, both the precursor lesions and also the molecular background of neoplastic progression need to be evalauated. In recent years, it was shown that colorectal carcinomas showing activating mutations in the KRAS gene (30-40% of the cases) are unresponsive to anti-EGFR therapy and that KRAS mutation analysis could predict patients for appropriate targeted therapy.In the present thesis, different precursor lesions of colorectal carcinoma (87 cases) together with the carcinoma cases (40 cases) were evaluated for KRAS and BRAF mutations in an attempt to correlate the morphologic findings with molecular results. Morphologic classificiaton was perfomed on the H&E sections where the lesion was marked with a marker pen to identify the area for DNA extraction. Following manual microdissection of these areas, DNA was isolated. KRAS mutation was assessed for exon 2 codon 12 ve 13, exon 3 codon 61 using pyrosequencing while BRAF mutations were evalauated using allele specific PCR and confirmed with DNA sequencing.Our results showed that, BRAF, together with KRAS, seem to play a significant role in colorectal neoplastic progression and in the development of serrated precursors of colorectal carcinoma, in particular. These findings suggest that BRAF may be used as a predictor in the targeted therapeutic approach to colorectal cancer patients.
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Kolorektal kanser, KRAS, BRAF mutasyon