Sarcoma Panel

Sarcoma is a rare and heterogeneous group of malignant tumors that arise from mesenchymal tissues, including bone, muscle, fat, and connective tissue. It accounts for about 1% of adult cancers but is more common in children and young adults.¹ Sarcomas are broadly classified into soft tissue sarcomas and bone sarcomas, with osteosarcoma typically arising in adolescence (average onset: 15-20 years), Ewing sarcoma in children and young adults (average onset: 10-20 years), and rhabdomyosarcoma in early childhood (average onset: 2-6 years).² In contrast, soft tissue sarcomas such as leiomyosarcoma and liposarcoma primarily affect older adults, with an average age of onset between 50 and 65 years.² Inherited sarcomas follow an autosomal dominant inheritance pattern, though with incomplete penetrance and variable expressivity, leading to different ages of onset and tumor types within affected families.³ Sarcomas do not show a strong ethnic predisposition, though some subtypes, such as Ewing sarcoma, are more common in individuals of European descent.⁴ This panel analyzes high-risk genes which can confer a substantially increased lifetime risk of sarcoma, moderate-risk genes which are associated with moderately increased lifetime risks, and genes for which there is emerging evidence of their risk for sarcoma compared to the general population. The diagnostic yield of this panel varies significantly by syndrome and clinical presentation.

All genetic tests have limitations. Please refer to our Test Methods page for limitations relevant to this methodology. 

EPCAM: Only copy number variant analysis is reported. 

DNA analysis of the PMS2 gene is complicated due to the presence of several pseudogenes. One particular pseudogene, PMS2CL, has high sequence similarity to PMS2 exons 11 to 15 (Blount et al. 2018. PubMed ID: 29286535). Next-generation sequencing (NGS) based copy number variant (CNV) analysis can detect deletions and duplications involving exons 1 to 10 of PMS2 but has less sensitivity for exons 11 through 15. Multiplex ligation-dependent probe amplification (MLPA) can detect deletions and duplications involving PMS2 exons 1 to 15. Of note, PMS2 MLPA is not typically included in this test but can be ordered separately using test code 6062, if desired. 

SDHA: Next Generation Sequencing analysis of this gene is technically challenging due to the presence of segmental duplications and paralogy. Therefore, analysis of CNVs in this gene is not included in this test. 

Enhanced Testing 

APC: This test includes APC promoter 1B. 

MSH2: This testing includes the inversion of exons 1 to 7 in MSH2 (Boland Inversion) and the c.942+3A>T polyalanine repeat variant.

NF1, PMS2: Deletion and duplication testing for NF1 and PMS2 is performed using NGS, but CNVs detected in these genes are usually confirmed via multiplex ligation- dependent probe amplification (MLPA). 

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.

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 in panel. Reportable variants include both sequence variants and NGS-based detection of copy number variants (CNVs). 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. 

If secondary findings are requested, only variants classified as pathogenic or likely pathogenic in genes within those categories will be reported.