Detection of K-ras mutations by a microelectronic DNA chip.

Abstract

The increased knowledge of the human genome, thanks to its sequencing and to the accumulation of data that ensue from it, prompts the characterization of disease-causing genes. Especially because of the continuing expansion of cancer-related gene discovery, oncobiology is a discipline that is undergoing rapid change. Detection of point mutations in oncogenes or tumor suppressor genes associated with the multistep process of oncogenesis could be of value in patient management. These potential molecular tumor markers are essential not only for the diagnosis, prognosis, or the follow-up of the disease but also for the management of therapy (,). Particularly, the K-ras protooncogene is altered, by point mutations within codons estimated to be critical for the biological activity of the protein (codons 12, 13, or 61), in a wide variety of tumors (). The incidence of these mutations can reach 95% in pancreatic carcinoma () and occurs in 40–60% of colorectal cancers, where they are associated with the progression from adenoma to carcinoma (). The detection of K-ras mutations enables the understanding of cancer biology and pathogenesis with, for example, a role in the mucinous differentiation pathway (). Alterations involving this oncogene may be of clinical importance because they can provide information for early diagnosis and clinical outcome. Their analysis within the tumor makes them of prognostic value (risk of relapse, mortality) (). Moreover, activation of the K-ras gene has been detected not only in the tumor but also in the stools () of patients with colorectal cancer.