ABSTRACT
ABSTRACT Cushing's disease (CD) is the most common cause of endogenous hypercortisolemia. The clinical management of this condition is complex and entails multiple therapeutic strategies, treatment of chronic comorbidities, and lifelong surveillance for recurrences and complications. The identification of robust, practical, and reliable markers of disease behavior and prognosis could potentially allow for a tailored and cost-efficient management of each patient, as well as for a reduction of the medical procedure-associated stress. For this purpose, multiple clinical, biochemical, imaging, histopathological, molecular, and genetic features have been evaluated over the years. Only a handful of them, however, have been sufficiently validated for their application in the routine care of patients with CD. This review summarizes the current status of the established and potential biomarkers of CD, bases for their use, proposed and/or established utility, as well as advantages and barriers for their implementation in the clinic.
ABSTRACT
Next-generation sequencing (NGS) is currently used in the clinical setting for targeted therapies and diagnosis of hematologic malignancies. Accurate detection of somatic variants is challenging because of tumor purity, heterogeneity, and the complexity of genetic alterations, with various issues ranging from high detection design to test implementation. This article presents guidelines developed through consensus among a panel of experts from the Korean Society for Genetic Diagnostics. They are based on experiences with the validation processes of NGS-based somatic panels for hematologic malignancies, with reference to previous international recommendations. These guidelines describe basic parameters with emphasis on the design of a validation protocol for NGS-based somatic panels to be used in practice. In addition, they suggest thresholds of key metrics, including minimum coverage, mean coverage with uniformity index, and minimum variant allele frequency, for the initial diagnosis of hematologic malignancies.