المؤلفون: Hoque MO; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Brait M, Rosenbaum E, Poeta ML, Pal P, Begum S, Dasgupta S, Carvalho AL, Ahrendt SA, Westra WH, Sidransky D

المصدر: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [J Thorac Oncol] 2010 Dec; Vol. 5 (12), pp. 1887-93.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 101274235 Publication Model: Print Cited Medium: Internet ISSN: 1556-1380 (Electronic) Linking ISSN: 15560864 NLM ISO Abbreviation: J Thorac Oncol Subsets: MEDLINE

مواضيع طبية MeSH: Epigenesis, Genetic* , Signal Transduction*, Carcinoma, Non-Small-Cell Lung/*genetics , ErbB Receptors/*genetics , Lung Neoplasms/*genetics , Proto-Oncogene Proteins B-raf/*genetics , Tumor Suppressor Proteins/*genetics, Adenocarcinoma/genetics ; Adult ; Aged ; Female ; Gene Dosage ; Genes, p53 ; Humans ; Male ; Middle Aged ; Mutation ; Oncogene Proteins v-erbB/metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins/genetics

مستخلص: Background: Prognosis for patients with non-small cell lung cancer (NSCLC) is poor. The potential value of modulating epidermal growth factor receptor (EGFR) for treatment is reflected by the recent approval of specific drugs that inhibit its activity. Mutations in EGFR were reported in lung cancer and generated interest, once they enable the identification of lung cancers likely to respond to various targeted small molecules.
Methods: We tested three key genetic and epigenetic alterations (EGFR, RASSF1A, and BRAF) of this pathway on a series of primary NSCLC (total 111; adenocarcinoma 49, squamous cell carcinoma [SCC] 48, and others 14). The mutational status of KRAS (and p53) was known for these samples. The purpose of this study was to define the pattern of erbB pathway alterations in NSCLC and to test for associations with clinical parameters.
Results: Five EGFR mutations were identified: three in adenocarcinoma (6%), one in SCC (2%), and one in adenocarcinoma with bronchoalveolar component tumor (7%). EGFR mutations included three in-frame deletions in exon 19 and two point mutations in exon 21. Promoter methylation of RASSF1A was detected in 25 of 45 adenocarcinomas and 18 of 46 SCC. Mutations of EGFR, BRAF, and KRAS in adenocarcinoma were mutually exclusive and inversely correlated with RASSF1A methylation (p = -0.394; p = 0.007).
Discussion: Overall, genetic and/or epigenetic alterations of erbB pathway genes were detected in 80% (39/49) of adenocarcinomas.Approximately half of primary adenocarcinoma harbor molecular alterations of the erbB pathway. Careful characterization of these alterations and response to anti-EGFR therapies is warranted to determine better and accurate determinants of clinical response.