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BMC Cancer  2009 

KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay

DOI: 10.1186/1471-2407-9-111

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Abstract:

The presence of KRAS mutations in codon 12 and 13 was analyzed in frozen and formalin-fixed paraffin-embedded (FFPE) tissue with a low density biochip platform. 381 malignant (29 borderline malignancy, 270 primary carcinomas, and 82 recurrent carcinomas) and 22 benign tissue samples from a total of 394 patients were examined. KRAS mutational status of each sample was correlated with dignity, FIGO stage, grade, histology, and survival.KRAS mutations were found in 60 (15%) samples with 58 samples deriving from malignant tissue and 2 samples deriving from benign tissue. In 55 (92%) samples codon 12 was found to be mutated. Frozen and FFPE samples concurred with respect to KRAS mutation status.KRAS mutation is a common event in ovarian cancer primarily in carcinomas of lower grade, lower FIGO stage, and mucinous histotype. The KRAS mutational status is no prognostic factor for patients treated with standard therapy. However, in line with experience from colorectal cancer and non-small-cell-lung cancer (NSCLC), it may be important for prediction of response to EGFR-targeted therapies.According to WHO statistics reported in 2005, ovarian cancer was ranked 5th in cancer related death in Europe.As in other tumors, the triggers of ovarian cancer involve genetic alterations and mutations. The discovery of underlying mechanisms that lead to an adverse patient outcome is of great importance.One of the best known DNA alterations in a variety of cancers is the mutational activation of ras protein family members. In fact, 20–30% of all human tumors harbour a mutation in a member of the ras family [1]. In ovarian cancer, KRAS mutations belong to the most frequently observed abnormalities [2].The ras proteins are small GTPases, downstream of EGFR, which normally cycle between their active and inactive state. In health, ras proteins are key components in many pathways that couple growth factor receptors to downstream mitogenic effectors involved in cell proliferation and differentiat

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