GENETIC TESTING TECHNOLOGIES

Genetic testing has changed dramatically since the discovery of the first cancer predisposition genes. This chapter includes descriptions of both older technologies, some of which are still in use today, and newer technologies, which have transformed clinical genetic testing. Older technologies include: linkage analysis; Sanger and Maxam Gilbert sequencing; Southern blotting; protein truncation testing; single strand conformation polymorphism; denaturing gradient gel electrophoresis; single nucleotide polymorphism technology; and allele-specific oligonucleotides. Seminal articles on cancer genetics may refer to these technologies, and families may still have older test results using these types of analyses. Newer technologies include: next-generation sequencing (NGS); multiplex ligation-dependent probe amplification; and array technology. The chapter describes common clinical issues including: how to assess the quality of NGS testing; what types of tests to order in varying circumstances; and how to handle variant classification, reclassification, and conflicting interpretations.