Genetic and epigenetic changes in primary metastatic and nonmetastatic colorectal cancer

Br J Cancer. 2006 Oct 23;95(8):1101-7. doi: 10.1038/sj.bjc.6603337. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cadherins / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics*
  • Neoplasm Metastasis
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins / genetics
  • ras Proteins / genetics


  • Cadherins
  • Cyclin-Dependent Kinase Inhibitor p16
  • RASSF1 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins B-raf
  • ras Proteins