Abstract 2121: High-resolution melting for detection of KRAS and EGFR mutations in tumors of the alimentary system

Abstract

Abstract The EGFR/Ras/Raf/MAPK pathway is one of the most important signal transduction pathways in cells. Dysregulation of this pathway is a common event in many cancers, including cancers of the alimentary system. EGFR and KRAS are two common genes in which mutations caused abnormal activation of the pathway. EGFR mutations are closely associated with a favorable response to treatment with tyrosine kinase inhibitors. KRAS mutations are associated with unresponsiveness to EGFR inhibitors. EGFR and KRAS mutation detection is important for carcinogenesis research and clinical therapy. Tumor tissue samples included 13 esophagus cancer, 52 gastric cancer and 67 colon cancer from a Chinese population. These were obtained from Dalian Medical University collection. High resolution melting (on a LightScanner™) was used to scan the mutations of KRAS exon 2, EGFR exon 19 and exon 21. All mutations detected by HRM were sequenced to identify the genotype. We found KRAS mutations in 5 (9.6%) patients with gastric cancer (2 with G12D; 1 with G12V; 2 with G13D) and 19 (28.4%) patients with colon cancers (11 with G12D, 3 with G12V, 4 with G13D; 1 with G13V). No KRAS mutations were found in esophagus cancer patients. The frequency of KRAS mutations in colon cancer was significantly higher than those in esophagus and gastric cancer (P<0.01). In 19 colon cancer patients with KRAS mutations, there were 6 (20.7%, 6/29) cases in the right colon (ascending colon and proximal 2/3 transverse colon) and 13 (34.2%, 13/38) cases in the left colon (distal 1/3 transverse colon, sigmoid colon and rectum). There is no significant difference in KRAS mutation frequencies between the right and the left colon. KRAS mutations were not associated with genders, ages, the invasive depth, lymph node metastasis and histopathological types in gastric and colon cancers. There were no EGFR exon 19 mutations found in any cases. EGFR exon 21 mutations were found in 2 gastric cancer patients (1 with L858R; 1 with G863D). In cancers of the alimentary system, KRAS mutations were more common than EGFR mutations, and KRAS mutations could be associated with the original tissues in the embryonic development. Namely, KRAS mutations were more common in cancers of organs from the midgut and hintgut than of those from the foregut, while EGFR mutations were all found in organs from the foregut. High resolution melting was a valuable method both in research and clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2121.