title: EGFR L2 domain mutation is not correlated with resistance to cetuximab in metastatic colorectal cancer patients.
abstract: BACKGROUND
  The KRAS mutation has been associated with resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in metastatic colorectal cancer (mCRC). However, the predictive biomarkers of cetuximab resistance in KRAS wild-type mCRC remain unknown except BRAF, NRAS, and PIK3CA exon 20. The objective of the study is to study the impact of EGFR L2 mutations on resistance to cetuximab in KRAS wild-type patients.
  
  
  METHODS
  A total of 247 mCRC patients were screened for KRAS status at the National Cancer Center Hospital between September 2008 and April 2010. We analyzed the EGFR L2 domain mutation status in KRAS wild type and in the patients treated with cetuximab-based therapy.
  
  
  RESULTS
  There were 136 patients with wild-type KRAS (55%). Sixty-five patients were analyzed for the L2 domain mutation status, and all patients received cetuximab-based therapy. One patient who had a mutation at exon 9 showed a partial response to cetuximab plus irinotecan.
  
  
  CONCLUSIONS
  Mutation of the EGFR L2 domain was analyzed in mCRC patients. Our findings do not provide sufficient evidence that EGFR L2 domain mutation is correlated with resistance to cetuximab.
authors.affiliation: Department of Clinical Oncology, Yamagata University, 2-2-2 Iidanishi, Yamagata, Yamagata, Japan. i.yuriko@med.id.yamagata-u.ac.jp
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Ito
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asada
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin