Dataset Information

ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients.

ABSTRACT: Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation. Therefore, liquid biopsy is an alternative or complementary method to tissue biopsy for the detection of some resistance mutations in EGFR arising during tyrosine kinase inhibitor treatment. Moreover, in some frail patients, or if the tumor lesion is not accessible to a tissue biopsy, a liquid biopsy can also detect some activating mutations in EGFR on initial assessment. Recent studies have evaluated the possibility of also using a liquid biopsy approach to detect an ALK rearrangement and/or the emergence during inhibitor treatment of some resistance mutations in ALK. These assessments can be performed by studying circulating tumor cells by fluorescent in situ hybridization and by immunocytochemistry and/or after the isolation of RNA from plasma samples, free or associated with platelets. Thus, the liquid biopsy may be a complementary or sometimes alternative method for the assessment of the ALK status in certain NSCLC patients, as well as a non-invasive approach for early detection of ALK mutations. In this review, we highlight the current data concerning the role of the liquid biopsy for the ALK status assessment for NSCLC patients, and we compare the different approaches for this evaluation from blood samples.

SUBMITTER: Hofman P

PROVIDER: S-EPMC5575609 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients.

Hofman Paul P

Cancers 20170812 8

Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase <i>ALK</i> gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has rec ...[more]

PMID: 28805673

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Project description:The analysis of tumours using biomarkers in blood is transforming cancer diagnosis and therapy. Cancers are characterised by evolving genetic alterations, making it difficult to develop reliable and broadly applicable DNA-based biomarkers for liquid biopsy. In contrast to the variability in gene mutations, the methylation pattern remains generally constant during carcinogenesis. Thus, methylation more than mutation analysis may be exploited to recognise tumour features in the blood of patients. In this work, we investigated the possibility of using global CpG (CpG means a CG motif in the context of methylation. The p represents the phosphate. This is used to distinguish CG sites meant for methylation from other CG motifs or from mentions of CG content) island methylation profiles as a basis for the prediction of cancer state of patients utilising liquid biopsy samples. We retrieved existing GEO methylation datasets on hepatocellular carcinoma (HCC) and cell-free DNA (cfDNA) from HCC patients and healthy donors, as well as healthy whole blood and purified peripheral blood mononuclear cell (PBMC) samples, and used a random forest classifier as a predictor. Additionally, we tested three different feature selection techniques in combination. When using cfDNA samples together with solid tumour samples and healthy blood samples of different origin, we could achieve an average accuracy of 0.98 in a 10-fold cross-validation. In this setting, all the feature selection methods we tested in this work showed promising results. We could also show that it is possible to use solid tumour samples and purified PBMCs as a training set and correctly predict a cfDNA sample as cancerous or healthy. In contrast to the complete set of samples, the feature selections led to varying results of the respective random forests. ANOVA feature selection worked well with this training set, and the selected features allowed the random forest to predict all cfDNA samples correctly. Feature selection based on mutual information could also lead to better than random results, but LASSO feature selection would not lead to a confident prediction. Our results show the relevance of CpG islands as tumour markers in blood.

Dataset Information

ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients.

Publications

ALK Status Assessment with Liquid Biopsies of Lung Cancer Patients.

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