Abstract

Over the past three decades, mortality from lung cancer has sharply and continuously increased in China, ascending to the first cause of death among all types of cancer. The ability to identify the actual sequence of gene mutations may help doctors determine which mutations lead to precancerous lesions and which produce invasive carcinomas, especially using next-generation sequencing (NGS) technology. In this study, we analyzed the latest lung cancer data in the COSMIC database, in order to find genomic “hotspots” that are frequently mutated in human lung cancer genomes. The results revealed that the most frequently mutated lung cancer genes are EGFR, KRAS and TP53. In recent years, EGFR and KRAS lung cancer test kits have been utilized for detecting lung cancer patients, but they presented many disadvantages, as they proved to be of low sensitivity, labor-intensive and time-consuming. In this study, we constructed a more complete catalogue of lung cancer mutation events including 145 mutated genes. With the genes of this list it may be feasible to develop a NGS kit for lung cancer mutation detection.

Highlights

  • Lung cancer is the most common cancer in terms of incidence and mortality throughout the world, accounting for 13% of all cases and for 18% of deaths in 2008 (Jemal et al, 2011)

  • Several mutated genes related to tumor growth, invasion or metastasis have been identified in lung cancer, and new agents that inhibit the activities of these genes have been developed, aiming to improve the outcome of lung cancer treatment (Dy and Adjei, 2002)

  • Using the methods described above, we obtained a complete list of lung cancer mutations comprising a total of 21,135 mutation events

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Summary

Introduction

Lung cancer is the most common cancer in terms of incidence and mortality throughout the world, accounting for 13% of all cases and for 18% of deaths in 2008 (Jemal et al, 2011). Several mutated genes related to tumor growth, invasion or metastasis have been identified in lung cancer, and new agents that inhibit the activities of these genes have been developed, aiming to improve the outcome of lung cancer treatment (Dy and Adjei, 2002). Among these genes, EGFR (epidermal growth factor receptor) is frequently overexpressed in non-small-cell lung cancer (NSCLC) (Rosell et al, 2009). A kit from Life Technologies Corporation (Ion Ampli SeqTM) was designed to detect 739 COSMIC mutations in 604 loci from 46 oncogenes and tumor suppressor genes, with emphasis on the deep coverage of genes KRAS, BRAF and EGFR for the detection of somatic mutations in archived cancer samples

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