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Biochip for K-ras mutation screening in ovarian cancer.

Ovarian carcinoma is the fifth most common female cancer type and the most common cause of death from gynecologic malignancies in the Western world (1). The three members of the ras gene family, H- ras , K- ras , and N- ras , are among the most common oncogenes associated with human neoplasms (2). Mutations in the K- ras gene are frequently found in malignant neoplasms: 90% of adenocarcinomas of the pancreas; 50% of colon, 30% of lung, and 50% of thyroid tumors; and 30% of myeloid leukemia cases, respectively (3). K- ras -activating mutations occur in codons 12 and 13 and seldom in codon 61, and lead to constitutive activation of the protein by increasing GDP/GTP exchange or decreasing GTPase activity of the protein, thus leading to increased cell proliferation.

K- ras mutation frequencies seem to be highly related to tumor histology. In general, K- ras mutations occur more frequently in mucinous tumors, including borderline malignancies, than in nonmucinous tumors such as serous carcinomas (4)(5)(6)(7)(8). K- ras mutations are more common in borderline serous tumors than in serous carcinomas, suggesting distinct etiologies (5)(9)(10)(11).

A biochip application for detection of the 10 most common mutations of K- ras codons 12 and 13 (12) combines mutant-enriched amplification with a highly specific hybridization protocol. The chip appears suitable for the detection of K- ras mutations in human feces (12). An improved biochip platform, called GeneStiX (ViennaLab Labordiagnostika GmbH), is designed to meet the needs of molecular diagnostic applications. Up to 400 different DNA capture oligonucleotides can be immobilized on the tip of a special plastic stick contained in a cylindrical tube. This allows hybridization with low volumes in a closed system (tube) and the use of standard …