A novel next generation sequencing approach to improve sarcoma diagnosis.
Mod Pathol
; 33(7): 1350-1359, 2020 07.
Article
in En
| MEDLINE
| ID: mdl-32047232
ABSTRACT
Sarcoma is a rare disease affecting both bone and connective tissue and with over 100 pathologic entities, differential diagnosis can be difficult. Complementing immune-histological diagnosis with current ancillary diagnostic techniques, including FISH and RT-PCR, can lead to inconclusive results in a significant number of cases. We describe here the design and validation of a novel sequencing tool to improve sarcoma diagnosis. A NGS DNA capture panel containing probes for 87 fusion genes and 7 genes with frequent copy number changes was designed and optimized. A cohort of 113 DNA samples extracted from soft-tissue and bone sarcoma FFPE material with clinical FISH and/or RT-PCR results positive for either a translocation or gene amplification was used for validation of the NGS method. Sarcoma-specific translocations or gene amplifications were confirmed in 110 out of 113 cases using FISH and/or RT-PCR as gold-standard. MDM2/CDK4 amplification and a total of 25 distinct fusion genes were identified in this cohort of patients using the NGS approach. Overall, the sensitivity of the NGS panel is 97% with a specificity of 100 and 0% failure rate. Targeted NGS appears to be a feasible and cost-effective approach to improve sarcoma subtype diagnosis with the ability to screen for a wide range of genetic aberrations in one test.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoma
/
Biomarkers, Tumor
/
Sequence Analysis, DNA
/
High-Throughput Nucleotide Sequencing
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mod Pathol
Journal subject:
PATOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
United kingdom