Anna Dellai1*, Alessandro Scandurra1 , Sonia Moretti2 , Martina Mandarano2 , Angelo Sidoni2 , Efisio Puxeddu2 , Cristina Kullmann3 , Maurizio Ferrari4 , Cristina Lapucci1 , Marcello Gambacorta5
Objective: Poorly Differentiated Thyroid Carcinomas (PDTC) and Anaplastic Thyroid Carcinoma (ATC) are different subtypes of thyroid carcinoma characterized respectively by a medium to high degree of dedifferentiation. These rare tumor types account for the majority of deaths from thyroid cancer, having usually a poor prognosis and short life expectancy. Diagnosis is not always straightforward due to the high degree of dedifferentiation of these tumors. Affected patients, on the other side, need for quick and targeted clinical answers for an effective treatment. Recent studies utilizing next generation sequencing have brought light into the molecular landscape of these tumors, providing evidences to support a stepwise progression from differentiated thyroid carcinomas to anaplastic thyroid carcinomas.
Methods: We tested Illumina TruSight Oncology 500 comprehensive genome panel platform on a preliminary set of 10 PDTC and 8 ATC FFPE samples for the identification of molecular landscape and genetic pathways involved and dysregulated in the tumorigenesis of PDTC and ATC. The assay evaluates at the same time DNA and RNA specific alterations and allows the analysis of important biomarkers for the response to immune-checkpoint inhibitor therapy as tumor mutational burden and microsatellite instability. After the sequencing pipeline, results were evaluated and shared with Pierian Dx Genomic Landscape, for the generation of a complete clinical report.
Results: We were able to identify Tier I, II and III variants for all analyzed samples, biomarker values and fusions, picturing a cancer specific profile which might be useful for a clinician to stratify patient with complicated diagnosis history, in a relatively short turnaround time.
Conclusion: With one single comprehensive profiling approach, we were able to investigate these aggressive and poorly characterized thyroid cancer subtypes, in a more comprehensive and faster fashion, providing clinicians with a complete clinical report allowing them to discuss the clinic and therapeutic applications of the retrieved data for patient management.