TEST:

NYU Langone Genome PACT assay

All cases of homozygous deletion detected by NGS were also detected by DNA methylation. DNA methylation derived copy number assessment is more sensitive for CDKN2A/B homozygous deletion than next generation sequencing.

Conclusions SF1 expressing PitNETs form a clinically and molecularly distinct tumor type characterized by hormonal silencing, tumor invasion, simple CNV profile, and hypomethylation. The gonadotrophic designation may not be clinically informative since they are all nonfunctioning.

Conclusions DNA methylation derived copy number assessment is more sensitive for CDKN2A/B homozygous deletion than next generation sequencing. This may be due to higher sensitivity of NGS to low tumor cell content for homozygous deletion calls.

However, our data suggest that brain tumor lesions classifying as DNT by DNA methylation with low score represent a diverse group. Furthermore, some FCD can classify as DNT, albeit with low calibrated score and require close correlation.

We conclude with presenting case studies that identify both the clinical utility and informatic challenges of variant calling specific to gene panel sequencing e.g., i) the capture of potential targetable rare and novel indels and multivariant mutations in exons 19 and 20 of EGFR, and ii) a unique KIT tandem duplication event in a gastrointestinal stromal tumor (GIST). We demonstrate the value in precision oncology for multiple cancer types and how the capture of unique variants can provide better targeted treatment options to cancer patients.

Conclusions We show that WGS using the non-coding DNA mutational signatures can detect ctDNA in low grade meningiomas in plasma despite low exonic mutational burden. ctDNA WGS could enable post-operative monitoring of meningiomas.

Aneuploidy is a more frequent molecular feature of aggressive oligodendroglioma. Therefore, genome wide assessment of aneuploidy may have a higher prognostic yield than targeted analysis of the CDKN2A/B locus.

Molecularly, PRNRP is a unique renal cell neoplasm defined by KRAS mutations and methylation patterns. KRAS mutation is an early event in this tumor type as illustrated by the small papillary adenoma. Methylation studies suggest that PRNRP is different from papillary RCC and may arise from the distal renal tubular epithelium.