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.
Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer / E. Miranda, A. Destro, A. Malesci, E. Balladore, P. Bianchi, E. Baryshnikova, G. Franchi, E. Morenghi, L. Laghi, L. Gennari, M. Roncalli. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - 95:8(2006 Oct 23), pp. 1101-1107.
|Titolo:||Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer|
MIRANDA, ELENA (Primo)
DESTRO, ANNARITA (Secondo)
RONCALLI, MASSIMO (Corresponding)
|Parole Chiave:||colorectal cancer; genetic and epigenetic alterations; metastogenic phenotype|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
Settore MED/12 - Gastroenterologia
Settore MED/09 - Medicina Interna
|Data di pubblicazione:||23-ott-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/sj.bjc.6603337|
|Appare nelle tipologie:||01 - Articolo su periodico|