Molecular characterization of patients with advanced lung adenocarcinoma at diagnosis with next generation sequencing by liquid biopsy in the Mexican population.

e21511 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tumor biopsy represents the standard for molecular diagnosis, nevertheless it is not always feasible to obtain. Liquid Biopsy (LB) may offer an alternative in the first line setting. Methods: Retrospective review of case files and next generation sequencing report (NGS) from LB from patients in a Validation Trial, performed from January 2018 to September 2019. We present the molecular alterations and clinical characteristics of the population. Results: 147 records and LB reports of patients 18 years and older with metastatic lung adenocarcinoma without prior treatment were included. 40% of the population had been selected based on a commercial local PCR test for EGFR (Idylla). 49% of them were female with Mean age of 60.9 ± 12.7. 56% had a history of smoking with an average packs/year of 20.5 (1-156) and 39% had exposure to wood smoke, 92% had an ECOG 0-1. 65 % of the Patients were diagnosed in Clinical Stage (8th Edition) IVA and 22% in IVB. 13% had SNC metastasis. The LB detected genomic alterations in 85.5% of the cases. 78% represent pathogenic mutations and 7.5% variants of uncertain significance (VUS).14.5% of the biopsies could not detect any ctDNA. The most frequent aberrations reported were TP53 in 51.7%, KRAS 16%, EGFR 16%, ALK 9%, PIK3CA 4%, RET 4%, BRAF 3%, BRCA 3, and HER2 3%. In addition, 20% had bTMB ≥10. Only 20% of the patients could receive a targeted therapy or immunotherapy of the potential ≈50%. Most cases had co-mutations (1-6 x case). Looking for factors associated with the presence of bTMB by a logistic regression model, it was possible to identify the presence of CNS metastases and smoking as identified with an OR of 3,688 (p = 0. 0.042) and 3.952 (p = 0. 024) respectively. Conclusions: It is feasible to have tumor molecular analysis through liquid biopsy in most cases, with genetic alterations previously reported in tumor tissue in the first line setting. [Table: see text]

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Targeted Next-Generation Sequencing Analysis for Recurrence in Early-Stage Lung Adenocarcinoma

Annals of Surgical Oncology ◽

10.1245/s10434-020-09276-x ◽

2020 ◽

Cited By ~ 1

Author(s):

In Ae Kim ◽

Jae Young Hur ◽

Hee Joung Kim ◽

Jung Hoon Park ◽

Jae Joon Hwang ◽

...

Keyword(s):

Next Generation Sequencing ◽

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Early Stage ◽

Genetic Alterations ◽

Smoking History ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Targeted Ngs ◽

Generation Sequencing

Abstract Background Despite surgical resection, early lung adenocarcinoma has a recurrence rate of 20–50%. No clear predictive markers for recurrence of early lung adenocarcinoma are available. Targeted next-generation sequencing (NGS) is rarely used to identify recurrence-related genes. We aimed to identify genetic alterations that can predict recurrence, by comparing the molecular profiles of patient groups with and without recurrence. Methods Tissues from 230 patients with resected stage I–II lung adenocarcinoma (median follow-up: 49 months) were analyzed via targeted NGS for 207 cancer-related genes. The recurrence-free survival according to the number and type of mutation was estimated using the Kaplan–Meier method. Independent predictive biomarkers related to recurrence were identified using the Cox proportional hazards model. Results Recurrence was observed in 64 patients (27.8%). In multivariate analysis adjusted for age, sex, smoking history, stage, surgical mode, and visceral pleural invasion, the CTNNB1 mutation and fusion genes (ALK, ROS1, RET) were negative prognostic factors for recurrence in early-stage lung adenocarcinoma (HR 4.47, p = 0.001; HR 2.73, p = 0.009). EGFR mutation was a favorable factor (HR 0.51, p = 0.016), but the CTNNB1/EGFR co-mutations were negative predictors (HR 19.2, p < 0.001). TP53 mutation was a negative predictor compared with EGFR mutation for recurrence (HR 5.24, p = 0.02). Conclusions: Targeted NGS can provide valuable information to predict recurrence and identify patients at high recurrence risk, facilitating selection of the treatment strategy among close monitoring and adjuvant-targeted therapy. Larger datasets are required to validate these findings.

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Detection of actionable gene mutations in breast cancer by amplicon-based next-generation sequencing liquid biopsy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1035 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1035-1035

Author(s):

Jing Shan Lim ◽

Yukti Choudhury ◽

Wai Min Phyo ◽

Chaitanya Gupta ◽

Yiliang Ho ◽

...

Keyword(s):

Breast Cancer ◽

Next Generation Sequencing ◽

Liquid Biopsy ◽

Tumor Tissue ◽

Pik3ca Mutation ◽

Genetic Alterations ◽

Driver Mutations ◽

Next Generation ◽

Pik3ca Mutations ◽

Generation Sequencing

1035 Background: The PI3K-inhibitor, alpelisib, was approved for the treatment of hormone receptor (HR)-positive, HER2-negative breast cancers with PIK3CA mutations based on findings from the SOLAR-1 trial. PIK3CA-positivity in tumor tissue was 29% (341/1172), but was only 15% (177/1172) in plasma cell-free DNA (cfDNA). The lower mutation detection rate observed in cfDNA may limit the clinical application of liquid biopsy in breast cancer. Amplicon-based next-generation sequencing (NGS) approach may confer improved sensitivity, allowing more effective profiling. We conducted a study to evaluate the use of this technology. Methods: Plasma cfDNA from 113 breast cancer patients (82.3% metastatic) underwent real-world testing in a CAP and ISO15189 accredited central laboratory. We analysed genetic alterations in cfDNA using an amplicon-based NGS technology. The presence of PIK3CA and other mutations relevant to breast cancer were correlated to molecular subtypes and treatment histories. Results: At least one mutation was detected in 70.8% of cases. Mutations were more frequent in metastatic cases (77.4%) compared to non-metastatic cases (27.3%). Across all patients, mutations in PIK3CA (33.6%), TP53 (32.7%), ESR1 (22.1%), GATA3 (7.1%) and ERBB2 (7.1%) were most frequently detected, in accordance with tumor tissue genotyping studies. PIK3CA mutations were more common in HR+ HER2- patients (44.4% vs 28.6% of other patients). Among PIK3CA-mutant cases, multiple PIK3CA mutations were present in 18.4% of cases, and hotspot mutations H1047R (34.2%), E542K (26.3%) and E545K (15.8%) were most frequent. An association was seen between PIK3CA mutation and prior treatment with CDK4/6 inhibitors (palbociclib, ribociclib) or mTOR inhibitor (everolimus), with 58% of PIK3CA-mutant cases having received these treatment previously compared to only 20% of PIK3CA-wild type (wt) cases. In addition, 75% of previously treated ESR1-mutant cases had specifically received hormonal treatment, compared to 60 % of ESR1-wt cases that received any treatment. Conclusions: We report similar PIK3CA mutation frequencies (~30%) with amplicon-based NGS on cfDNA compared to tumor tissue testing in breast cancer. Importantly, other driver mutations were also observed at similar frequencies as external tissue studies, implying high sensitivity as the primary reason for performance. This supports the clinical utility of an amplicon-based NGS-based approach to liquid biopsy for the sensitive detection of actionable mutations in breast cancer.

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Liquid Biopsy, ctDNA Diagnosis through NGS

Life ◽

10.3390/life11090890 ◽

2021 ◽

Vol 11 (9) ◽

pp. 890

Author(s):

Chen Lin ◽

Xuzhu Liu ◽

Bingyi Zheng ◽

Rongqin Ke ◽

Chi-Meng Tzeng

Keyword(s):

Next Generation Sequencing ◽

Cancer Diagnosis ◽

Liquid Biopsy ◽

Sampling Bias ◽

Circulating Tumor Dna ◽

Genetic Alterations ◽

Great Promise ◽

Next Generation ◽

Minimal Invasion ◽

Generation Sequencing

Liquid biopsy with circulating tumor DNA (ctDNA) profiling by next-generation sequencing holds great promise to revolutionize clinical oncology. It relies on the basis that ctDNA represents the real-time status of the tumor genome which contains information of genetic alterations. Compared to tissue biopsy, liquid biopsy possesses great advantages such as a less demanding procedure, minimal invasion, ease of frequent sampling, and less sampling bias. Next-generation sequencing (NGS) methods have come to a point that both the cost and performance are suitable for clinical diagnosis. Thus, profiling ctDNA by NGS technologies is becoming more and more popular since it can be applied in the whole process of cancer diagnosis and management. Further developments of liquid biopsy ctDNA testing will be beneficial for cancer patients, paving the way for precision medicine. In conclusion, profiling ctDNA with NGS for cancer diagnosis is both biologically sound and technically convenient.

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Cytology meets next generation sequencing and liquid biopsy: A case of lung adenocarcinoma presenting as metastasis to the phalanx

Diagnostic Cytopathology ◽

10.1002/dc.24438 ◽

2020 ◽

Vol 48 (8) ◽

pp. 759-764 ◽

Cited By ~ 1

Author(s):

Eduardo Clery ◽

Pasquale Pisapia ◽

Ilaria Migliatico ◽

Francesco Pepe ◽

Caterina De Luca ◽

...

Keyword(s):

Next Generation Sequencing ◽

Lung Adenocarcinoma ◽

Liquid Biopsy ◽

Next Generation ◽

Generation Sequencing

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Faculty Opinions recommendation of Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718014371.793495250 ◽

2014 ◽

Author(s):

Jean-Pascal Machiels

Keyword(s):

Squamous Cell Carcinoma ◽

Next Generation Sequencing ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Genetic Alterations ◽

Neck Squamous Cell Carcinoma ◽

Next Generation ◽

Targeted Next Generation Sequencing ◽

Generation Sequencing

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A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next- Generation Sequencing

Current Bioinformatics ◽

10.2174/1574893615666200324133451 ◽

2020 ◽

Vol 15 ◽

Author(s):

Zheng Jiang ◽

Hui Liu ◽

Siwen Zhang ◽

Jia Liu ◽

Weitao Wang ◽

...

Keyword(s):

Next Generation Sequencing ◽

Microsatellite Instability ◽

Liquid Biopsy ◽

Tumor Tissue ◽

High Sensitivity ◽

Next Generation ◽

Tissue Samples ◽

Next Generation Sequencing Technology ◽

Medication Selection ◽

Generation Sequencing

Background: Microsatellite instability (MSI) is a prognostic biomarker used to guide medication selection in multiple cancers, such as colorectal cancer. Traditional PCR with capillary electrophoresis and next-generation sequencing using paired tumor tissue and leukocyte samples are the main approaches for MSI detection due to their high sensitivity and specificity. Currently, patient tissue samples are obtained through puncture or surgery, which causes injury and risk of concurrent disease, further illustrating the need for MSI detection by liquid biopsy. Methods: We propose an analytic method using paired plasma/leukocyte samples and MSI detection using next-generation sequencing technology. Based on the theoretical progress of oncogenesis, we hypothesized that the microsatellite site length in plasma equals the combination of the distribution of tumor tissue and leukocytes. Thus, we defined a window-judgement method to identify whether biomarkers were stable. Results: Compared to traditional PCR as the standard, we evaluated three methods in 20 samples (MSI-H:3/MSS:17): peak shifting method using tissue vs. leukocytes, peak shifting method using plasma vs. leukocytes, and our method using plasma vs. leukocytes. Compared to traditional PCR, we observed a sensitivity of 100%, 0%, and 100%, and a specificity of 100.00%, 94.12%, and 88.24%, respectively. Conclusion: Our method has the advantage of possibly detecting MSI in a liquid biopsy and provides a novel direction for future studies to increase the specificity of the method.

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