Hotspot Mutations Detectable by Next-generation Sequencing in Exhaled Breath Condensates from Patients with Lung Cancer

Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways—either via mutations or genomic amplification—confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of PIK3CA in aggressive cancers, most of the available data highlight the important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways are investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of PI3K/AKT/mTOR pathways in major cancer types and examines its association with clinicopathological parameters and prognosis.

show abstract

“…PIK3CA gene amplifications have been reported in lung cancer [59,60]. The frequency of PIK3CA gene mutation in lung cancer varies significantly.…”

Section: Prognostic Role Of Pik3ca Gene Mutation In Lung Cancermentioning

confidence: 99%

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Alqahtani

Ayesh

Halawani

2019

Cancers

View full text Add to dashboard Cite

show abstract

“…76 In recent years, the success rate of NGS testing on EBC-DNA samples have opened a new era of genomics and molecular biology in lung cancer. 31,32 Obviously, these findings could provide a promising noninvasive method for the determination of the genetic profiles of each tested individual.…”

Section: Nuclear Genes Mutationsmentioning

confidence: 96%

“…The synchronous analysis of the metabolites such as lipid and protein as well as the nucleic acid in exhaled breath can be so promising for disease early diagnosis, and monitoring the treatment efficiency of respiratory diseases such as lung cancer. 31,32 The main purpose of this review is to summarize recent achievements in the analysis of EBC from the genetics point of view. Obviously, the molecular analysis of EBC can be a surrogate and promising technique for tracking genetic alterations and molecular profiling in lung diseases.…”

Section: Introductionmentioning

confidence: 99%

Exhaled Breath Condensate: A Non-Invasive Source for Tracking of Genetic and Epigenetic Alterations in Lung Diseases

et al. 2020

View full text Add to dashboard Cite

Lung diseases have been recognized as an extensive cause of morbidity and mortality in the worldwide. The high degree of clinical heterogeneity and nonspecific initial symptoms of lung diseases contribute to a delayed diagnosis. So, the molecular and genomic profiling play a pivotal role in promoting the pulmonary diseases. Exhaled breath condensate (EBC) as a novel and potential method for sampling the respiratory epithelial lining fluid is to assess the inflammatory and oxidative stress biomarkers, drugs and genetic alterations in the pathophysiologic processes of lung diseases. The recent studies on the analysis of EBC from both a genetic and epigenetic point of view were searched from database and reviewed. This review provides an overview of the current findings in the tracking of genomic and epigenetic alterations which are potentially effective in better management of cancer detection. In addition, respiratory microbiota DNA using EBC samples in association with pulmonary disease especially lung cancer were investigated. Various studies have concluded that EBC has a great potential for analysis of nuclear and mitochondrial DNA alterations as well as epigenetic modifications and identification of respiratory microbiome. Next-generation sequencing (NGS) based genomic profiling of EBC samples is recommended as a promising approach to establish personalized based prevention, diagnosis, treatment and post-treatment follow-ups for patients with lung diseases especially lung cancer.

show abstract

“…exhaled breath condensate (EBC) and urine, have also been tested as alternatives to liquid biopsy (9)(10)(11)(12). We previously reported the detection of EGFR exon 19 deletion (Ex19del) mutations in EBC by conventional polymerase chain reaction (PCR) (13).…”

Section: Detection Of Epidermal Growth Factor Receptor Mutations In Ementioning

confidence: 99%

Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction

et al. 2020

View full text Add to dashboard Cite

The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non-small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube™ method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC-ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54-81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post-operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC-ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC-ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC-ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult.

show abstract

Hotspot Mutations Detectable by Next-generation Sequencing in Exhaled Breath Condensates from Patients with Lung Cancer

Cited by 21 publications

References 21 publications

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Exhaled Breath Condensate: A Non-Invasive Source for Tracking of Genetic and Epigenetic Alterations in Lung Diseases

Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction

Contact Info

Product

Resources

About