Dataset Information

Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay.

ABSTRACT: Circulating tumor DNA (ctDNA) has shown great promise as a minimally invasive liquid biopsy for personalized cancer diagnostics especially among metastatic patients. Here, we used a novel sensitive assay to detect clinically relevant mutations in ctDNA in blood plasma from metastatic non-small cell lung cancer (NSCLC) patients, including patients with a limited oligo-brain metastatic disease. We analyzed 66 plasma samples from 56 metastatic NSCLC patients for 74 hotspot mutations in five genes commonly mutated in NSCLC using a novel MassARRAY-based lung cancer panel with a turnaround time of only 3 days. Mutations in plasma DNA could be detected in 28 out of 56 patients (50.0%), with a variant allele frequency (VAF) ranging between 0.1% and 5.0%. Mutations were detected in 50.0% of patients with oligo-brain metastatic disease, although the median VAF was lower (0.4%) compared to multi-brain metastatic patients (0.9%) and patients with extra-cranial metastatic progression (1.2%). We observed an overall concordance of 86.4% (n = 38/44) for EGFR status between plasma and tissue. The MassARRAY technology can detect clinically relevant mutations in plasma DNA from metastatic NSCLC patients including patients with limited, oligo-brain metastatic disease.

SUBMITTER: Belloum Y

PROVIDER: S-EPMC7690267 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay.

Belloum Yassine Y Janning Melanie M Mohme Malte M Simon Ronald R Kropidlowski Jolanthe J Sartori Alexander A Irwin Darryl D Westphal Manfred M Lamszus Katrin K Loges Sonja S Riethdorf Sabine S Pantel Klaus K Wikman Harriet H

Cells 20201022 11

Circulating tumor DNA (ctDNA) has shown great promise as a minimally invasive liquid biopsy for personalized cancer diagnostics especially among metastatic patients. Here, we used a novel sensitive assay to detect clinically relevant mutations in ctDNA in blood plasma from metastatic non-small cell lung cancer (NSCLC) patients, including patients with a limited oligo-brain metastatic disease. We analyzed 66 plasma samples from 56 metastatic NSCLC patients for 74 hotspot mutations in five genes c ...[more]

PMID: 33105541

Similar Datasets

Project description:The aim of this study was to assess the frequency of potentially actionable genomic alterations in breast cancer that could be targeted with approved agents or investigational drugs in clinical trials using a next-generation sequencing-based genomic profiling assay performed in a Clinical Laboratory Improvement Amendments-certified and College of American Pathologists-accredited commercial laboratory. Methods. Fifty-one breast cancers were analyzed, including primary tumor biopsies of 33 stage I-II and 18 stage IV cancers (13 soft tissue, 3 liver, and 2 bone metastases). We assessed 3,230 exons in 182 cancer-related genes and 37 introns in 14 genes often rearranged in cancer for base substitutions, indels, copy number alterations, and gene fusions. The average median sequencing depth was 1,154×. Results. We observed 158 genomic alterations in 55 genes in 48 of 51 (94%) tumors (mean 3.1, range 0-9). The average number of potentially therapeutically relevant alterations was similar in primary (1.6, range 0-4) and in heavily pretreated metastatic cancers (2.0, range 0-4) (p = .24). The most common actionable alterations were in PIK3CA (n = 9, phosphatidylinositol 3-kinase [PI3K]/mammalian target of rapamycin [mTOR] inhibitors), NF1 (n = 7, PI3K/mTOR/mitogen-activated protein kinase inhibitors), v-akt murine thymoma viral oncogene homolog 1-3 (n = 7, PI3K/mTOR/AKT inhibitors), BRCA1/2 (n = 6, poly[ADP-ribose] polymerase inhibitors), and CCND1,2 and CCNE (n = 8)/cycline dependent kinase (CDK)6 (n = 1) (CDK4/6 inhibitors), KIT (n = 1, imatinib/sunitinib), ALK (n = 1, crizotinib), FGFR1,2 (n = 5, fibroblast growth factor receptor inhibitors), and EGFR (n = 2, epidermal growth factor receptor inhibitors). Our sequencing assay also correctly identified all six cases with HER2 (ERBB2) amplification by fluorescence in situ hybridization when tumor content was adequate. In addition, two known activating HER2 mutations were identified, both in unamplified cases. Conclusion. Overall, 84% of cancers harbored at least one genomic alteration linked to potential treatment options. Systematic evaluation of the predictive value of these genomic alterations is critically important for further progress in this field.

Dataset Information

Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay.

Publications

Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets