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. 2019 Aug 16;11(8):1196.
doi: 10.3390/cancers11081196.

Development, Implementation and Assessment of Molecular Diagnostics by Next Generation Sequencing in Personalized Treatment of Cancer: Experience of a Public Reference Healthcare Hospital

Javier Simarro  1   2 , Rosa Murria  1   2 , Gema Pérez-Simó  1   2 , Marta Llop  1 , Nuria Mancheño  3 , David Ramos  3 , Inmaculada de Juan  1   2 , Eva Barragán  1 , Begoña Laiz  1 , Enrique Cases  4 , Emilio Ansótegui  4 , José Gómez-Codina  2   5 , Jorge Aparicio  2   5 , Carmen Salvador  2   5 , Óscar Juan  5 , Sarai Palanca  6   7
Affiliations

Development, Implementation and Assessment of Molecular Diagnostics by Next Generation Sequencing in Personalized Treatment of Cancer: Experience of a Public Reference Healthcare Hospital

Javier Simarro et al. Cancers (Basel). .

Abstract

The establishment of precision medicine in cancer patients requires the study of several biomarkers. Single-gene testing approaches are limited by sample availability and turnaround time. Next generation sequencing (NGS) provides an alternative for detecting genetic alterations in several genes with low sample requirements. Here we show the implementation to routine diagnostics of a NGS assay under International Organization for Standardization (UNE-EN ISO 15189:2013) accreditation. For this purpose, 106 non-small cell lung cancer (NSCLC) and 102 metastatic colorectal cancer (mCRC) specimens were selected for NGS analysis with Oncomine Solid Tumor (ThermoFisher). In NSCLC the most prevalently mutated gene was TP53 (49%), followed by KRAS (31%) and EGFR (13%); in mCRC, TP53 (50%), KRAS (48%) and PIK3CA (16%) were the most frequently mutated genes. Moreover, NGS identified actionable genetic alterations in 58% of NSCLC patients, and 49% of mCRC patients did not harbor primary resistance mechanisms to anti-EGFR treatment. Validation with conventional approaches showed an overall agreement >90%. Turnaround time and cost analysis revealed that NGS implementation is feasible in the public healthcare context. Therefore, NGS is a multiplexed molecular diagnostic tool able to overcome the limitations of current molecular diagnosis in advanced cancer, allowing an improved and economically sustainable molecular profiling.

Keywords: UNE-EN ISO 15189 accreditation; metastatic colorectal cancer; molecular diagnostics; next generation sequencing; non-small cell lung cancer.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Distribution of gene alterations in NSCLC (green) and mCRC patients (blue). Column chart in the upper part represents the total number of mutations for each sample. Left column indicates the percentage of samples with specific gene alteration. Dark grey—Not tested. R—Rearrangements.
Figure 2
Figure 2
Circos diagram. Associations among the most prevalently mutated genes in NSCLC patients.
Figure 3
Figure 3
Circos diagram. Associations among the most prevalently mutated genes in mCRC patients.
Figure 4
Figure 4
Percentage of NSCLC patients with actionable alterations detected by NGS. Fifty-eight percent of patients included in the study were susceptible to being treated with targeted drugs approved in advanced cancers or in clinical trials.
Figure 5
Figure 5
Classification of mCRC patients according to clinically relevant alterations detected by NGS.
See this image and copyright information in PMC

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