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Medline ® Abstract for Reference 37

of 'Molecular genetics of colorectal cancer'

37
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Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer.
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Miranda E, Destro A, Malesci A, Balladore E, Bianchi P, Baryshnikova E, Franchi G, Morenghi E, Laghi L, Gennari L, Roncalli M
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Br J Cancer. 2006;95(8):1101. Epub 2006 Sep 12.
 
Colorectal cancer (CRC) develops as multistep process, which involves genetic and epigenetic alterations. K-Ras, p53 and B-Raf mutations and RASSF1A, E-Cadherin and p16INK4A promoter methylation were investigated in 202 CRCs with and without lymph node and/or liver metastasis, to assess whether gene abnormalities are related to a metastogenic phenotype. K-Ras, B-Raf and p53 mutations were detected in 27, 3 and 32% of the cases, with K-Ras mutations significantly associated with metastatic tumour (P=0.019). RASSF1A, E-Cadherin and p16INK4A methylation was documented in 20, 44 and 33% of the cases with p16INK4A significantly associated with metastatic tumours (P=0.001). Overall, out of 202 tumours, 34 (17%) did not show any molecular change, 125 (62%) had one or two and 43 (21%) three or more. Primary but yet metastatic CRCs were prevalent in the latter group (P=0.023) where the most frequent combination was one genetic (K-Ras in particular) and two epigenetic alterations. In conclusion, this analysis provided to detect some molecular differences between primary metastatic and nonmetastatic CRCs, with K-Ras and p16INK4A statistically altered in metastatic tumours; particular gene combinations, such as coincidental K-Ras mutation with two methylated genes are associated to a metastogenic phenotype.
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Molecular Genetics Laboratory, Istituto Clinico Humanitas, University of Milan, Via Manzoni 56, Rozzano, Milano 20089, Italy.
PMID