Using Large-Scale Genomics Data to Identify Driver Mutations in Lung Cancer: Methods and Challenges

Hudson, Andrew M.; Wirth, Christopher; Stephenson, Natalie L.; Fawdar, Shameem; Brognard, John

doi:10.2217/pgs.15.60

Cited by 15 publications

(9 citation statements)

References 86 publications

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“…A recent investigation has addressed that mutation rate was higher in the genes coding for proteins of longer length. For example, extremely long genes such as TTN have a high mutational frequency (52%) in lung squamous TCGA data [ 52 ]. Therefore, further study is required to clarify the biological meaning of these alterations.…”

Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

et al. 2018

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PurposeThe identification of genomic alterations related to recurrence in early-stage non-small cell lung cancer (NSCLC) patients may help better stratify high-risk individuals and guide treatment strategies. This study aimed to identify the molecular biomarkers of recurrence in early-stage NSCLC.ResultsOf the 42 tumors evaluable for genomic alterations, TP53 and EGFR were the most frequent alterations with population frequency 52.4% and 50.0%, respectively. Fusion genes were detected in four patients, which had lower mutational burden and relatively better genomic stability. EGFR mutation and fusion gene were mutually exclusive in this study. CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were only observed in the relapsed patients. Increased copy number alteration index was observed in early relapsed patients. Among these genomic alterations, early-stage NSCLCs harboring CDKN2A, FAS, SUFU and SMARCA4 genomic alterations were found to be significantly associated with recurrence. Some of these new findings were validated using The Cancer Genome Atlas (TCGA) dataset.ConclusionsThe genomic alterations of CDKN2A, FAS, SUFU and SMARCA4 in early-stage NSCLC are found to be associated with recurrence, but confirmation in a larger independent cohort is required to define the clinical impact.Materials and MethodsPaired primary tumor and normal lung tissue samples were collected for targeted next-generation sequencing analysis. A panel targets exons for 440 genes was used to assess the mutational and copy number status of selected genes in three clinically relevant groups of stage I/II NSCLC patients: 1) Early relapse; 2) Late relapse; and 3) No relapse.

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Section: Discussionmentioning

confidence: 99%

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

et al. 2018

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“…Similarly, EGFR mutationd were more frequently observed in the non-smoking Asian population than in the Western population. Up to 59.7% of East Asian never or light smokers had tumors harboring an EGFR mutation while only 11% of the Western patients with lung adenocarcinoma possessed an EGFR mutation [ 156 , 157 ]. The variable frequencies of certain variants between different ethnic groups bring into question the applicability of the same gene panels to be used across all populations.…”

Section: Part Ii: Roles Of Somatic Mutations In Cancer Pharmacogenomimentioning

confidence: 99%

The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics

2019

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Cancer pharmacogenomics is the science concerned with understanding genetic alterations and its effects on the pharmacokinetics and pharmacodynamics of anti-cancer drugs, with the aim to provide cancer patients with the precise medication that will achieve a good response and cause low/no incidence of adverse events. Advances in biotechnology and bioinformatics have enabled genomic research to evolve from the evaluation of alterations at the single-gene level to studies on the whole-genome scale using large-scale genotyping and next generation sequencing techniques. International collaborative efforts have resulted in the construction of databases to curate the identified genetic alterations that are clinically significant, and these are currently utilized in clinical sequencing and liquid biopsy screening/monitoring. Furthermore, countless clinical studies have accumulated sufficient evidence to match cancer patients to therapies by utilizing the information of clinical-relevant alterations. In this review we summarize the importance of germline alterations that act as predictive biomarkers for drug-induced toxicity and drug response as well as somatic mutations in cancer cells that function as drug targets. The integration of genomics into the medical field has transformed the era of cancer therapy from onesize-fits-all to cancer precision medicine.

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“…The most common mutation is in the Kirsten rat sarcoma (KRAS) oncogene, occurring in approximately 30% of adenocarcinomas (Ade) predominantly in patients with a history of smoking [5]. BRAF is mutated in approximately 3% of patients (with half of cases being the V660E mutation) [6]. Along with KRAS and BRAF, epidermal growth factor receptor (EGFR) mutations were discovered in patients with Ade and small cell lung cancer (SCLC) [5].…”

Section: The Molecular Landscape Of Lung Cancer 21 Gene Mutationsmentioning

confidence: 99%

Molecular Biology of Lung Cancer and Future Perspectives for Screening

Tarro¹,

Paolini²,

Rossi³

2019

Mass Spectrometry - Future Perceptions and Applications

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Lung cancer patients have the highest mortality among patients with solid tumors worldwide and their prognosis is strictly stage-associated. However, only 15-20% of patients are diagnosed in stage I, since these early tumors are frequently asymptomatic. Early detection of lung cancer, which allows effective therapeutic intervention, is a promising approach to lowering its mortality rate. However, conventional diagnostic methods for lung cancer, such as chest X-ray and CT of the chest, produce high costs and potentially false-positive results. Thus, the discovery of highly sensitive, specific, noninvasive, and cost-effective lung cancer biomarkers combined with conventional approaches, such as X-rays, may improve the sensitivity of lung cancer screening. Herein, we summarize the most recent studies about the molecular pathology of lung cancer and discuss the advancements expected in the near future, including the potential biomarkers and liquid biopsy approaches for the detection of lung cancer in populations at risk of developing this disease.

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Using Large-Scale Genomics Data to Identify Driver Mutations in Lung Cancer: Methods and Challenges

Cited by 15 publications

References 86 publications

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer

The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics

Molecular Biology of Lung Cancer and Future Perspectives for Screening

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