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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
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KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay.

Veronika Auner1, Gernot Kriegshäuser, Dan Tong

  • 1Division of Gynaecology, Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria. veronika.auner@meduniwien.ac.at

BMC Cancer
|April 11, 2009
PubMed
Summary

KRAS mutations are common in ovarian cancer, particularly in lower-grade and mucinous types. While not a prognostic factor for standard therapy, KRAS status may predict response to EGFR-targeted treatments.

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Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • KRAS gene mutations are frequent in ovarian carcinoma.
  • These mutations are relevant due to emerging epidermal growth factor receptor (EGFR)-targeted therapies.
  • KRAS mutations are linked to poor response and resistance to EGFR inhibitors.

Purpose of the Study:

  • To investigate the spectrum of KRAS mutations in ovarian carcinoma.
  • To understand the prevalence and characteristics of KRAS mutations in different ovarian tissue types.

Main Methods:

  • Analyzed KRAS mutations in codons 12 and 13 using a biochip platform.
  • Examined 394 tissue samples (381 malignant, 22 benign) including frozen and FFPE tissues.
  • Correlated KRAS mutational status with clinicopathological factors and survival.

Main Results:

  • KRAS mutations were identified in 15% (60/394) of samples, predominantly in malignant tissues (58/60).
  • Codon 12 was the most frequently mutated site (92% of mutations).
  • Frozen and FFPE samples showed consistent KRAS mutation status.

Conclusions:

  • KRAS mutation is common in ovarian cancer, especially in lower grade, lower FIGO stage, and mucinous histotypes.
  • KRAS mutational status does not appear to be a prognostic factor for standard therapy.
  • KRAS status may be predictive of response to EGFR-targeted therapies, similar to findings in colorectal and non-small-cell lung cancer.