A novel next generation sequencing approach to improve sarcoma diagnosis

Lauren McConnell, Oisín Houghton, Peter Stewart, Jana Gazdova, Shambhavi Srivastava, Chang Kim, Mark Catherwood, Anna Strobl, Adrienne M Flanagan, Anca Oniscu, Leonie I Kroeze, Patricia Groenen, Philippe Taniere, Manuel Salto-Tellez, David Gonzalez

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
255 Downloads (Pure)


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.

Original languageEnglish
JournalModern Pathology
Early online date11 Feb 2020
Publication statusEarly online date - 11 Feb 2020


Dive into the research topics of 'A novel next generation sequencing approach to improve sarcoma diagnosis'. Together they form a unique fingerprint.

Cite this