Molecular Testing of Lung Cancers

Shim, Hyo Sup; Choi, Yoon‐La; Kim, Lucia; Chang, Sunhee; Kim, Wan-Seop; Roh, Mee Sook; Kim, Taejung; Ha, Seung Yeon; Chung, Jin-Haeng; Jang, Se Jin; Lee, Geon Kook

doi:10.4132/jptm.2017.04.10

Cited by 32 publications

(24 citation statements)

References 92 publications

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“…In particular, epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and ROS proto-oncogene 1 (ROS1) rearrangements have been frequently used as therapeutic targets, and they are regarded as "must-test" biomarkers in the molecular diagnostics of advanced-stage lung cancer patients [1]. Currently, single-gene assays, such as real-time polymerase chain reaction (PCR), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) tests, are considered the gold standard for selecting eligible patients for EGFR-, ALK-, and ROS1-specific TKI therapy [1,2]. However, with the development of next-generation sequencing (NGS), other less common oncogenic alterations with available therapies have been detected [3].…”

Section: Introductionmentioning

confidence: 99%

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Park

Shim

2020

Cancer Res Treat

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PurposeEpidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use. Materials and MethodsPatients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared. ResultsA total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31). ConclusionEven though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.

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Section: Introductionmentioning

confidence: 99%

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Park

Shim

2020

Cancer Res Treat

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“…O relatório é uma parte essencial de qualquer teste de laboratório e deve por isso conter toda a informação necessária para que o médico requisitante, bem como, o paciente saiba exatamente que estudo foi realizado e qual o seu resultado. Os relatórios de patologia molecular devem incluir informação do paciente, do material biológico utilizado para a análise, da entidade requisitante do exame, descrição do método molecular utilizado (incluindo genes/exões estudados, sensibilidade e especificidade analítica), limitações do próprio método, resultados do teste, uma contextualização dos achados moleculares, bem como, comentário de algum aspeto pré -analítico, analítico ou pós -analítico, que possa influenciar a interpretação clínica dos resultados 10,66 . Este deve conter uma linguagem clara, simples e direta, sem incluir quaisquer informações dúbias.…”

Section: Relatório Validação De Testes E Garantia Da Qualidadeunclassified

Patologia molecular em cancro do pulmão: Evolução e contributos

Piña¹,

Pinto²,

Domingues³

et al. 2020

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“…However, its clinical utility is limited due to the requirement for specimens with a high ratio of tumour to normal cells. Samples with <20% of mutant allele frequency (corresponding to a minimum tumour cell content of 40% assuming complete heterozygosity) may be considered inadequate for testing or risk a false positive result . The ongoing improvement in NGS technologies and their capacity for detecting low‐frequency variants in small diagnostic samples means that direct sequencing is now considered inadequate for routine testing.…”

Section: Direct Sequencingmentioning

confidence: 99%

Somatic mutations and immune checkpoint biomarkers

et al. 2019

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The development of molecular testing for identifying somatic mutations and immune checkpoint biomarkers has directed treatment towards personalized medicine for patients with non‐small cell lung cancer. The choice of molecular testing in a clinical setting is influenced by cost, expertise in the technology, instrumentation setup and sample type availability. The molecular techniques described in this review include immunohistochemistry (IHC), fluorescent in situ hybridization, direct sequencing, real‐time polymerase chain reaction (PCR), denaturing high‐performance liquid chromatography, matrix‐assisted laser desorption/ionization time of flight mass spectrometry and next‐generation sequencing (NGS). IHC is routinely used in clinical practice for the classification, differentiation, histology and identification of targetable alterations of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed death ligand‐1 (PD‐L1). Recently, the PD‐L1 pathway was identified as being exploited by tumour cells, allowing immune resistance and tumour evasion. The development of immune checkpoint inhibitors as treatment for tumours expressing checkpoints has highlighted the need for standardized IHC assays to inform treatment decisions for patients. Direct sequencing was historically the gold standard for mutation testing for EGFR, KRAS (Kirsten rat sarcoma viral oncogene homologue) and BRAF (v‐Raf murine sarcoma viral oncogene homologue B1) requiring a high ratio of tumour to normal cells, but this has been superseded by more sensitive methods. NGS is a new emerging technique, which allows high‐throughput coverage of frequently mutated genes, including less common BRAF and MET mutations and alterations in tumour suppressor genes. When an NGS platform is unavailable, PCR‐based technologies offer an efficient and cost‐effective single gene test to guide patient treatment. This article will review these techniques and discuss the future of molecular platforms underpinning clinical management decisions.

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Molecular Testing of Lung Cancers

Cited by 32 publications

References 92 publications

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing

Patologia molecular em cancro do pulmão: Evolução e contributos

Somatic mutations and immune checkpoint biomarkers

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