Abstract
IntroductionThe identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient–tumor sample pairs. MethodsClinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient–tumor samples. ResultsOf these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. ConclusionsThe frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC.
Highlights
The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC
In White patients, the frequencies of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fluorescence in situ hybridization (FISH) positivity decreased with increasing pack-year cohorts; while the frequencies of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations increased
In Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort
Summary
The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. The most prevalent mutated or rearranged oncogenes identified NSCLCs are v-ki-ras Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), among others [1;2]. In most United States-based academic medical practices that treat NSCLC the population of patients seen is mixed with a variety of heterogeneous racial groups and smoking habits; and the frequency of common driver oncogenes in tumors from these patients is not well defined using commercially-available genotyping techniques. We sought to better elucidate how self-reported race and smoking status affected the frequency of somatic tumor genotype aberrations of NSCLCs in an academic medical practice based in Boston (Massachusetts in the United States) that sees a heterogeneous group of patients afflicted with NSCLC
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