Seeking Amyloidosis Very Early: Free light Chain Differentials and IGLV Gene Use as Screening Variables for Light-chain Amyloidosis in λ Monoclonal Gammopathies.

Background: Early diagnosis of systemic light-chain amyloidosis (AL) is needed because 25% of patients die within months of diagnosis. In patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) of the λ isotype, we explored the use of 2 screening variables: a free light chain difference of 23mg/L between λ and k and presence of IGLV genes that occur more frequently in AL.

Methods: Patients contacted us and we sent HIPAA release and consent forms for discussion by phone.

Genetic and Phenotypic Intra-Clade Variation in Candida auris Isolated from Critically Ill Patients in a New York City Tertiary Care Center.

Background: Candida auris is an emerging multidrug-resistant pathogen. Interpretation of susceptibility testing can be difficult since minimum inhibitory concentration (MIC) breakpoints have not been fully established.

Methods: All C.

Benchmarking bioinformatics approaches for tumour mutational burden evaluation from a large cancer panel against whole-exome sequencing.

Tumour mutational burden (TMB) is used to predict response to immunotherapies. Although several groups have proposed calculation methods for TMB, a clear consensus has not yet emerged. In this study, we explored TMB calculation approaches with a 586-gene cancer panel (1.

Detection of mitochondrial DNA (mtDNA) mutations.

The maternally inherited mitochondrial DNA (mtDNA) is a circular 16,569bp double stranded DNA that encodes 37 genes, 24 of which (2 rRNAs and 22 tRNAs) are necessary for transcription and translation of 13 polypeptides that are all subunits of respiratory chain. Pathogenic mutations in mtDNA cause respiratory chain dysfunction, and are the underlying defect in an ever-increasing number of mtDNA-related encephalomyopathies with distinct phenotypes. In this chapter, we present an overview of mtDNA mutations and describe the molecular techniques currently employed in our laboratory to detect two types of mtDNA mutations: single-large-scale rearrangements and point mutations.

Microsatellite instability detection using a large next-generation sequencing cancer panel across diverse tumour types.

Aim: Microsatellite instability (MSI), a hallmark of DNA mismatch repair deficiency, is a key molecular biomarker with multiple clinical implications including the selection of patients for immunotherapy, identifying patients who may have Lynch syndrome and predicting prognosis in patients with colorectal tumours. Next-generation sequencing (NGS) provides the opportunity to interrogate large numbers of microsatellite loci concurrently with genomic variants. We sought to develop a method to detect MSI that would not require paired normal tissue and would leverage the sequence data obtained from a broad range of tumours tested using our 467-gene NGS Columbia Combined Cancer Panel (CCCP).

Precision Medicine in Children and Young Adults with Hematologic Malignancies and Blood Disorders: The Columbia University Experience.

Background: The advent of comprehensive genomic profiling has markedly advanced the understanding of the biology of pediatric hematological malignancies, however, its application to clinical care is still unclear. We present our experience integrating genomic data into the clinical management of children with high-risk hematologic malignancies and blood disorders and describe the broad impact that genomic profiling has in multiple aspects of patient care.

Methods: The Precision in Pediatric Sequencing Program at Columbia University Medical Center instituted prospective clinical next-generation sequencing (NGS) for high-risk malignancies and blood disorders.

Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations.

Background: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated.

Methods: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure.