Molecular profiling of non-small cell lung cancer

Abstract

Lung cancer is generally treated with conventional therapies, including chemotherapy and radiation. These methods, however, are not specific to cancer cells and instead attack every cell present, including normal cells. Personalized therapies provide more efficient treatment options as they target the individual's genetic makeup. The goal of this study was to identify the frequency of causal genetic mutations across a variety of lung cancer subtypes in the earlier stages. 833 samples of non-small cell lung cancer from 799 patients who received resection of their lung cancer, were selected for molecular analysis of six known mutations, including EGFR, KRAS, BRAF, PIK3CA, HER2 and ALK. A SNaPshot assay was used for point mutations and fragment analysis searched for insertions and deletions. ALK was evaluated by IHC +/-FISH. Statistical analysis was performed to determine correlations between molecular and clinical/pathological patient data. None of the tested variants were identified in most (66.15%) of cases. The observed frequencies among the total samples vs. only the adenocarcinoma cases were notable different, with the highest frequency being the KRAS mutation (24.49% vs. 35.55%), followed by EGFR (6.96% vs. 10.23%), PIK3CA (1.20% vs. 0.9%), BRAF (1.08% vs. 1.62%), ALK (0.12% vs. 0.18%), while the lowest was the HER2 mutation (0% for both). The statistical analysis yielded correlations between presence of a mutation with gender, cancer type, vascular invasion and smoking history. The outcome of this study will provide data that helps stratify patient prognosis and supports development of more precise treatments, resulting in improved outcomes for future lung cancer patients.

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective

“…Concerning drug utilization, this study found that, among patients with non-squamous NSLCL, women received first-line target therapy more than twice as frequently as men (14.9% vs. 6.5%). These data are in line with the frequency of lung cancer mutations in the Caucasian population, where EGFR and BRAF mutations are known to be more frequent in women [ 16 , 17 , 18 ].…”

A retrospective observational study of the natural history of advanced non–small-cell lung cancer in patients with KRAS p.G12C mutated or wild-type disease

“…Other studies have also demonstrated that nonsquamous cell carcinoma is the most common histology type associated with KRAS mutations in general, as well as KRAS p.G12C specifically [30,33]. Although KRAS mutations may be relatively uncommon in some phenotypes, with a recent study finding a prevalence of only 4.4 % in squamous cell carcinoma [33], KRAS p.G12C mutations can be found across patient types (eg, in nonsmokers [34]); thus, broad molecular testing is needed to identify KRAS p.G12C status in all patients with NSCLC.…”

Profiling non-small cell lung cancer reveals that PD-L1 is associated with wild type EGFR and vascular invasion, and immunohistochemistry quantification of PD-L1 correlates weakly with RT-qPCR

“…Our group has recently profiled a large Nova Scotian lung cancer patient cohort for major driver mutations in lung cancer ( EGFR , ALK , KRAS , BRAF , and PIK3CA ) [ 20 ]. Here we assess the relationship between clinicopathological data, driver mutations, and PD-L1 expression in the expanded patient cohort.…”