title: Spatial and temporal genetic heterogeneity of epidermal growth factor receptor gene status in a patient with non-small cell lung cancer: a case report.
abstract: BACKGROUND
  To date, an epidermal growth factor receptor-activating mutation is recognized as a genetic hallmark that predicts a good response to treatment with epidermal growth factor receptor tyrosine kinase inhibitor. However, there has been less long-term observation of the mutational status within the same patient. To the best of our knowledge, this is the first case report which illustrates the instability of the genetic status of pulmonary adenocarcinoma cells.
  
  
  METHODS
  A 64-year-old Japanese woman with advanced lung adenocarcinoma had been undergoing various anticancer treatments, including epidermal growth factor receptor tyrosine kinase inhibitor, for seven years. She had been receiving locoregional treatment in addition to systemic treatment. She maintained a good performance status until seven years after the initial diagnosis, although she had local and distant recurrences. We analyzed the genetic status of the epidermal growth factor receptor gene in a series of specimens obtained from various tumor-containing lesions throughout the therapeutic period. The results of the genetic analyses clearly showed that the spatial and temporal genetic heterogeneity of the epidermal growth factor receptor gene status originated from an identical tumor ancestor.
  
  
  CONCLUSIONS
  An alternative paradigm to determine a therapeutic strategy for a patient with lung cancer should be considered given the genetic heterogeneity and instability of tumor cells.
authors: First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. shimizto@takii.kmu.ac.jp.
authors: Makoto
authors: M
authors: Ogata
authors: Toshiki
authors: T
authors: Shimizu
authors: Takashi
authors: T
authors: Yokoi
authors: Shosaku
authors: S
authors: Nomura