title: Assessment of intratumoral heterogeneity of oncogenic driver mutations in surgically-resected lung adenocarcinoma: implications of percutaneous biopsy-based molecular assay for target-directed therapy.
abstract: OBJECTIVE
  The present study investigated whether there is intratumoral heterogeneity of oncogenic driver mutations within surgically-resected tumors and between surgical specimens and percutaneous biopsy samples.
  
  
  METHODS
  Thirty-four patients who underwent surgery for lung adenocarcinoma were studied. We obtained four to five snap-frozen samples from each surgical specimen. Mutational analyses of epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit-alpha (PIK3CA) genes were performed and then compared in multiple surgical specimens and between surgical and percutaneous biopsy samples.
  
  
  RESULTS
  EGFR and KRAS mutations were detected in 19 and 2 patients, respectively. Multiple surgical samples from different areas of the tumor had the same mutation genotype in all cases except for one. The 14 biopsy specimens had the same mutational profiles as the corresponding surgical specimens.
  
  
  CONCLUSIONS
  Heterogeneous distributions of oncogenic driver mutations were not found in surgically-resected lung adenocarcinoma. Small tumor specimens obtained with percutaneous biopsy were suitable for EGFR analyses, thus providing critical information for personalized therapy.
authors: Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, Korea. Tel: +82 234106896, jhingookkim@gmail.com.
authors: Hong Kwan
authors: HK
authors: Kim
authors: Ho Yun
authors: HY
authors: Lee
authors: Yoon-La
authors: YL
authors: Choi
authors: So-Jung
authors: SJ
authors: Choi
authors: Haejoo
authors: H
authors: Choi
authors: Jinseon
authors: J
authors: Lee
authors: Joungho
authors: J
authors: Han
authors: Myung-Ju
authors: MJ
authors: Ahn
authors: Kyung Soo
authors: KS
authors: Lee
authors: Jhingook
authors: J
authors: Kim
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D001706:Biopsy; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D018773:Genes, erbB-1; D011905:Genes, ras; D018740:Genetic Heterogeneity; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: 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
keywords: Intratumoral heterogeneity; lung adenocarcinoma; oncogenic driver mutations