Ibrahim Boga, Turkey
Cukurova Uinversity AGENTEM (Adana Genetic Diseases Diagnosis and Treatment Center)Presenter of 1 Presentation
A MULTI-GENE PANEL TEST COULD HELP US HOW TO APPROACH A PID PATIENT FOR MALIGNANCIES
Abstract
Background and Aims
Primary immunodeficiencies (PIDs) are often associated with malignancies due to lack of immune response to cancerous cells. Next-generation-sequencing (NGS) is a great success of genetic testing to identify specific genes that, when altered, confer clinically recognized traits such as cancer susceptibility. Thus, it becomes a clinically useful tools to test a patient for both PID diagnosis and enables predictive genetic testing. In this our case-based review, a multi-gene panel NGS based testing offers significant benefits even though a benign variant in relation to PID might be related to susceptibility for malignancies.
Methods
We performed next-generation-sequencing (MiSeq, Illumina) via a customized multi-gene panel including 18 genes related to SCID (severe combined immunodeficiency) (IL7R,LIG4,RAG1,AK2,FOXN1,JAK3,CTPS1,CORO1A,PTPRC,PRKDC,RAG2,DCLRE1C,CD3D,IL2R, ADA,NHEJ1,CD247,PNP) from peripheral blood samples of clinically SCID diagnosed patients.
Results
As a result of our multi-gene panel NGS testing we detect heterozygous p.T414M and p.V138I variants in IL7R gene which is classified as benign according to ACMG (American Collage of Medical Genetics) criteria for SCID phenotype. However, these under specified variants are also related to lynch syndrome and myeloid neoplasms.
Conclusions
Multi-gene panels via NGS offer significant benefits however, with complications of main three uncertainties (1) the penetrance of cancer risk (2) the scope of cancer risk (3) the clinical relevance of variants which the spectrum of normalcy is not well defined. To sum up, skilled genetic testing laboratory for both molecular diagnostics and immunodeficiencies are crucial to design and to determine the clinical and society value of multi-gene panel testing via NGS technologies.