Genetic analysis of multiple synchronous lesions of the colon adenoma-carcinoma sequence.

作者: R Sedivy , B Wolf , M Kalipciyan , G G Steger , J Karner-Hanusch

DOI: 10.1054/BJOC.1999.1091

关键词: AdenocarcinomaPathologyColorectal cancerBiologyCancerAberrant crypt fociCarcinogenesisSingle-strand conformation polymorphismColon AdenomaMicrosatellite instability

摘要: The colorectal adenoma–carcinoma sequence represents a well-known paradigm for the sequential development of cancer driven by accumulation genomic defects. Although is well investigated, studies about tumours different dignity co-existent in same patient are seldom. In order to address distribution genetic alterations lesions patient, we coincidently investigated carcinomas, adenomas and aberrant crypt foci patients with sporadic colon cancer. By utilizing polymerase chain reaction, single-strand conformation polymorphism, heteroduplex-analysis, restriction fragment length protein truncation test sequencing techniques looked mutations microsatellite instability APC, H- ras, K- p53, DCC DNA repair genes hMLH1/hMSH2. accordance suggested colon, four reflected progressive defects synchronously appearing during carcinogenesis. However, two non-hereditary malignomas presented instabilities but suggesting non-clonal growth under almost identical conditions environment. Thus, sporadically manifesting multiple were not necessarily similar mechanisms. Premalignant may transform into malignant starting from types instability, which indicates independent simultaneous tumorigenesis within organ. © 2000 Cancer Research Campaign

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