Comprehensive Endocrine Cancer Panel

About the Comprehensive Endocrine Cancer Panel   

Hereditary endocrine tumor syndromes can cause the overproduction of hormones and predispose individuals to the development of endocrine neoplasms. Syndromes primarily affecting endocrine and neuroendocrine tissues include multiple endocrine neoplasia types 1, 2, and 4 (caused by pathogenic variants in the MEN1, RET, and CDKN1B genes), familial isolated pituitary adenoma (AIP), Carney complex (PRKAR1A), and hyperparathyroidism-jaw tumor syndrome (CDC73). Other syndromes affecting endocrine and neuroendocrine tissue in their clinical spectrum include Von Hippel-Lindau disease (VHL), familial adenomatous polyposis (APC), Li-Fraumeni syndrome (TP53), PTEN hamartoma tumor syndrome (PTEN), neurofibromatosis 1 (NF1), and DICER1 syndrome (DICER1).^1-11 Of note, RET variants can also be associated with Hirschsprung disease. These conditions follow primarily autosomal dominant inheritance patterns, and both sequence variants and copy number variants can be causative. This comprehensive panel is designed to identify potentially causative germline variants for these endocrine neoplasms in many sites, including thyroid, parathyroid, and pancreas, and across multiple tumor types, including paraganglioma/pheochromocytoma (PGL/PCC), adrenocortical carcinoma (ACC), and neuroblastoma. The diagnostic yield of this panel will vary based on the clinical phenotype and family history of the patient.  

The analytical sensitivity of the PGxome platform has been validated at >99% for single nucleotide variants, >95% for indels <49 bp, and >99% for CNV ≥3 exons in size. Sensitivity is reduced in regions with repetitive elements or paralogy.  The analytical sensitivity of the PGnome platform has been validated at >99% for sequence variants and >99% for structural variants (SV) 1kb-10Mb in size. Sensitivity is reduced in regions with repetitive elements or paralogy. 

PGxome® platform: Capture and amplification based Next Generation Sequencing (NGS) is used to sequence the coding regions of nearly all genes and immediate flanking non-coding DNA (± 10 bp) in all available transcripts along with other non-coding regions harboring known disease-causing variants. Results are filtered to defined genes on the panel. Reportable variants include both sequence variants and NGS-based detection of copy number variants (CNVs).  PGnome® platform: PCR-free Next Generation Sequencing (NGS) is used to sequence the coding regions of nearly all genes as well as intronic and intergenic regions. Detailed variant analysis and interpretation is focused on the coding exons and ± 10 bp into introns. Genomic variants outside of these coding regions are not investigated unless warranted (for example, if a gene of interest is highlighted by the provider, or if a single-hit pathogenic variant is found in a recessive gene). Results are filtered to defined genes on the panel. Reportable variants include sequence variants; NGS-based detection of structural variants (SV), including copy number variants (CNVs) and inversions; and repeat expansion variants in currently available relevant genes.  Variants not meeting our quality threshold through NGS alone are confirmed with an orthogonal method, including but not limited to Sanger and array.  All variants within the analyzed genes which are classified as pathogenic, likely pathogenic, risk, or variant of uncertain significance will be reported.