Frequent Mutations in EGFR, KRAS and TP53 Genes in Human Lung Cancer Tumors Detected by Ion Torrent DNA Sequencing

Abstract

Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

Genetic alteration profiling of patients with resected squamous cell lung carcinomas

“…Clinical success with combination targeted therapy depends on the identification of molecular abnormalities for co-administration of a single or combination of target agents against the detected therapeutic targets [41]. In our study, the results indicated that the co-occurrence of mutation (17.8%) or copy number alterations (38.2%) were identified in a significant proportion of tumor samples.…”

The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer

“…This approach can detect thousands of single-nucleotide variations and rearrangements-and although the same specific single-nucleotide variation mutations (e.g., in EGFR and Kirsten rat sarcoma viral homolog gene [KRAS]) are often found in different patients, identical breakpoints in genetic rearrangements have not been detected among different patients. 87,88 Finally whole-exome or whole-genome sequencing has been proposed, but it suffers from being expensive, not being applicable for rearrangements, being hard to implement in the clinic, and having limited sensitivity as currently available.…”

Identification of Independent Primary Tumors and Intrapulmonary Metastases Using DNA Rearrangements in Non–Small-Cell Lung Cancer

“…22 The additional commonality of many recurrent SNV mutations, such as EGFR and KRAS, means they are often shared even between independent tumors. 23 In contrast, the probability of detecting an identical somatic chromosomal breakpoint in two unrelated tumors is extremely unlikely, if not zero. The common TMPRSS2-ERG fusion is observed in approximately 50% of patients with prostate cancer.…”