Čačev T et al. (2005) NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer. Gut 54: 1129–1135

Aberrant activation of Ras is involved in the development of a range of cancers. The NF1 gene product, neurofibromin, acts as a tumor suppressor by 'switching off' the active form of Ras and therefore has a potential role in tumorigenesis.

In this first study of the potential role of NF1 in sporadic colon cancer, Čačev and colleagues investigated loss of heterozygosity at the NF1 locus and NF1/mRNA expression in 100 samples of tumor and adjacent normal tissue obtained during routine surgery for colon adenocarcinoma.

Loss of heterozygosity of NF1 was seen in only 20.7% of heterozygous samples, and the authors concluded that this event is not important in the development or progression of sporadic colon cancer. The differential expression of NF1 isoforms during tumorigenesis, however, might be more important in the regulation of NF1 function. There was a statistically significant increase in NF1 mRNA expression in tumor tissue compared with normal tissue (P = 0.04), with NF1 isoform type II predominantly expressed in normal tissue, and type I predominant in tumor tissues (P = 0.0005). A continuous transition from predominant type II expression in normal tissue to predominant type I expression in tumor tissue was also detected. Total neurofibromin expression increased as tumors advanced, but total wild-type neurofibromin remained the same.

The authors conclude that NF1 might play a role in the development and progression of colon cancer and that this gene could be a potential tumor marker and new potential target for therapy.