title: Identification of KRAS and PIK3CA but not BRAF mutations in patients with gastric cancer.
abstract: Cetuximab, an immunoglobulin G1 chimeric monoclonal antibody directed against the epidermal growth factor receptor, is currently considered to be the strategy with the most potential for the treatment of gastric cancer due to the low frequency of KRAS mutations in patients with gastric cancer. However, the therapeutic success of cetuximab in colorectal cancer (CRC) has demonstrated that the clinical effect of cetuximab is closely dependent not only on KRAS mutations, but also BRAF and phosphoinositide-3-kinase, catalytic, α polypeptide (PIK3CA) mutations. In the present study, the status of KRAS, BRAF and PIK3CA mutations in gastric cancer were investigated concomitantly in order to aid the selection of patients eligible for treatment with cetuximab. Mutations in KRAS (exon 2), BRAF (exon 15) and PIK3CA (exon 9 and exon 20) were retrospectively evaluated by high resolution melting analysis and DNA direct sequencing in samples from 156 patients with gastric cancer. Mutations in either KRAS or PIK3CA were identified in 13 samples (8.3%), 7 samples with KRAS mutations and 6 samples with PIK3CA mutations. No mutations in the BRAF gene were identified. The frequency of mutations in either KRAS or PIK3CA were significantly higher in patients without lymph node metastasis than those with. Furthermore, KRAS and PIK3CA mutations were mutually exclusive. The present study, therefore, suggested that it may be necessary to evaluate KRAS and PIK3CA mutations concomitantly for the selection of patients eligible for treatment with cetuximab.
authors: Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Weipeng
authors: W
authors: Lu
authors: Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Hong
authors: H
authors: Wei
authors: Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Mei
authors: M
authors: Li
authors: Department of Pathology, The Third People's Hospital of Dalian, Dalian, Liaoning 116000, P.R. China.
authors: Hai
authors: H
authors: Wang
authors: Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Lina
authors: L
authors: Liu
authors: Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Qiuping
authors: Q
authors: Zhang
authors: Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Lisha
authors: L
authors: Liu
authors: Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China.
authors: Shen
authors: S
authors: Lu
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D000068818:Cetuximab / Q000627:therapeutic use; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D059645:Mutation Rate; D060787:Neoplasm Grading; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab