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Molecular diagnostics for lung cancer is a well-established standard of care, but how to use the available diagnostic tools for optimal and cost-effective patient care remains unresolved. Here, we show that DNA-only, small gene next-generation sequencing (sNGS) panels (<50 genes) combined with ultra-rapid reflex testing for common fusion transcripts using the Idylla Genefusion assay provide a cost-effective and sufficiently comprehensive testing modality for the majority of lung cancer cases. We also demonstrate the need for additional reflex testing capability on larger DNA and fusion panels for a small subset of lung cancers bearing rare single-nucleotide variants, indels and fusion transcripts and secondary, post-treatment resistance mutations. A similar testing workflow could be adopted for other solid tumor types for which extensive gene/fusion variant profiles are available both in the treatment-naïve and post-therapy settings.

The PARK2 gene is located on 6q26, encodes ubiquitin-E3- ligase, and is a transcriptional repressor of p53. It contains 12 exons. PARK2 copy number variants has been reported in various types of neurodevelopmental disorders, namely schizophrenia, Parkinson's disease (PD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). In this retrospective study, nine cases (five with microdeletion and four with microduplication) are reported with 6q26 deletion disrupting the PARK2 gene. Microdeletion sizes ranged between 215 Kb and 356 Kb, and duplication between 279 Kb and 726 Kb. These were present within the exons 7-10. Family follow up with FISH probes revealed paternal inheritance in two cases, maternal in two cases, and de novo origin in one case. Our results support previous studies showing that patients with PARK2 CNVs involving exons 5-12 might be more deleterious and cause a unique syndrome. Comprehensive analysis of additional case studies is needed to have a full characterization of this neurological disorder syndrome.

Testing of tumors by next generation sequencing (NGS) is impacted by relatively long turnaround times and a need for highly trained personnel. Recently, Idylla oncology assays were introduced to test for BRAF , EGFR , KRAS , and NRAS common hotspot mutations that do not require specialized trained personnel. Moreover, the interpretation of results is fully automated, with rapid turnaround time. Though Idylla testing and NGS have been shown to have high concordance in identifying EGFR , BRAF , KRAS , and NRAS hotspot mutations, there is limited experience on optimal ways the Idylla system can be used in routine practice. We retrospectively evaluated all cases with EGFR , BRAF , KRAS , or NRAS mutations identified in clinical specimens sequenced on two different NGS panels at the University of Rochester Medical Center (URMC) molecular diagnostics laboratory between July 2020 and July 2021 and assessed if these mutations would be detected by the Idylla cartridges if used. We found that the Idylla system could accurately identify Tier 1 or 2 actionable genomic alterations in select associated disease pathologies if used. Yet, in a minority of cases, we would have been unable to detect NGS-identified pathogenic mutations due to their absence on the Idylla panels. We derived algorithmic practice guidelines for the use of the Idylla cartridges. Overall, Idylla molecular testing could be implemented either as a first-line standalone diagnostic tool in select indications or for orthogonal confirmation of uncertain results.