Publications (2)8.11 Total impact
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Article: Analysis of driver mutations in female non-smoker asian patients with pulmonary adenocarcinoma.
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ABSTRACT: Previous studies have revealed that EGFR mutation and/or EML4-ALK gene fusion rate was higher in the non-smoker Asian females with pulmonary adenocarcinoma. The aim of this study is to determine the distribution of known oncogenic driver mutations in the female non-smoker Asian patients with pulmonary adenocarcinoma. 104 consecutively resected lung adenocarcinomas from 396 non-smoker females (less than 100 cigarettes in a lifetime) at a single institution (Tongji University, Shanghai, China) were analyzed for mutations in EGFR, EML4-ALK, KRAS, HER2, BRAF, and PIK3CA. 73 (70.2 %) tumors harbored EGFR mutations; among these, 28 were deletions in exon 19, 44 were L858R missense changes, and eight were T790M mutations. 10 (9.6 %) harbored EML4-ALK fusions, two harbored KRAS mutations, two harbored BRAF mutations, and two harbored PI3K mutations. A majority of the mutations were mutually exclusive, except two with EGFR mutation and BRAF mutation, one with EML4-ALK fusions and PI3K mutation. Thus, 82.7 % (86 of 104; 95 % CI, 75.4-90.0 %) of lung adenocarcinomas from non-smoker females were found to harbor the well-known oncogenic mutations in five genes. Lung cancer in non-smoking Asian females is a distinct entity, with majority of this subgroup being developed by the oncogenic mutations. The prospective mutation examination in this population will be helpful for devising a targeted therapy for a majority of the patients.Cell biochemistry and biophysics 06/2012; 64(2):155-60. · 3.34 Impact Factor -
Article: Association of EGFR mutation or ALK rearrangement with expression of DNA repair and synthesis genes in never-smoker women with pulmonary adenocarcinoma.
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ABSTRACT: BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement may predict the outcome of targeted drug therapy and also are associated with the efficacy of chemotherapy in patients with nonsmall cell lung cancer (NSCLC). The authors of this report investigated the relation of EGFR mutation or ALK rearrangement status and the expression of DNA repair or synthesis genes, including excision repair cross-complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthetase (TS), and breast cancer-early onset (BRCA1), as a potential explanation for these observations. METHODS: In total, 104 resected lung adenocarcinomas from women who were nonsmokers were analyzed concurrently for EGFR mutations, ALK rearrangements, and mRNA expression of the ERCC1, RRM1, TS, and BRCA1 genes. EGFR mutations were detected with a proprietary detection kit, ALK rearrangements were detected by polymerase chain reaction analysis, and genetic mRNA expression was detected by real-time polymerase chain reaction analysis. RESULTS: Of 104 patients, 73 (70.2%) had EGFR mutations, and 10 (9.6%) had ALK rearrangements. ERCC1 mRNA levels in patients who had EGFR mutations were 3.44 ± 1.94 × 10(-3) , which were significantly lower than the levels in patients who were positive for ALK rearrangements and in patients who were negative for both biomarkers (4.60 ± 1.95 × 10(-3) and 4.95 ± 2.33 × 10(-3) , respectively; P = .010). However, TS mRNA levels were significantly lower in patients who had EGFR mutations (1.15 ± 1.38 × 10(-3) vs 2.69 ± 3.97 × 10(-3) ; P = .006) or ALK rearrangements (1.21 ± 0.78 × 10(-3) vs 2.69 ± 3.97 × 10(-3) ; P = .020) than in patients who were negative for both biomarkers. CONCLUSIONS: NSCLC specimens that harbored activating EGFR mutations were more likely to express low ERCC1 and TS mRNA levels, whereas patients with NSCLC who had ALK rearrangement were more likely to express low TS mRNA levels. Cancer 2012. © 2012 American Cancer Society.Cancer 05/2012; · 4.77 Impact Factor
