Di Shao:
Development and application of a next generation sequencing based cancer genomic profiling assay to guide treatment decisions in lung cancer

Date: 28-02-2018    Supervisor: Karsten Kristiansen



Lung cancer genomic profiling has become an important tool to facilitate the use of targeted agents and has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can still be technically challenging. We developed a targeted next generation sequencing (NGS) technology-based assay for rapid characterization of clinical actionable mutations. Next, using 61 retrospective formalin-fixed and paraffin-embedded (FFPE) samples and 5 cancer cell lines, the reliability and limit of detection were assessed by comparing the results with those obtained by conventional methods. NGS showed great potential for analysis of tumor mutation in several genes and multiple types of samples simultaneously.

With the well-validated assay, we attempted to describe the mutation landscape of lung cancer in people of Chinese ethnicity and to provide important insights to the profile of oncogenic mutations in this group. By comparing mutation prevalence of lung adenocarcinoma (ADC) between East Asians and Caucasians, we demonstrated that the Asian ethnicity had a significantly different prevalence of known somatic mutations when compared with Caucasians.

Furthermore, we investigated the diagnostic performance of pleural effusion as a specimen for molecular analysis. We compared EGFR, KRAS, and ALK mutation results obtained from 30 thoracic biopsy samples and matched pleural effusion samples, using ARMS PCR and NGS. Our findings indicate that pleural effusion is a feasible source of tumor DNA for identifying patients who can benefit from the targeted therapy.

Finally, we evaluated the detection performance using matched tumor DNA (tDNA) and plasma from patients with advanced stage NSCLC. Our results showed high concordance in the detection of clinically actionable alterations found in tumor tissues and paired plasma samples. Our findings demonstrated that targeted NGS using plasma is a feasible approach for accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.