Abstract 3914
Background
Sarcoma is a rare disease affecting both bone and connective tissue and with over 100 pathologic entities, diagnosis can be difficult. Approximately one third of sarcoma patients however are characterised by recurrent genetic alterations mainly chromosomal translocations, which result in fusion genes, and gene amplifications. Fusion genes are highly useful diagnostic markers and are currently identified in the clinical setting using FISH/RT-PCR. Conversely, conclusive results cannot be achieved in up to 25% of fusion positive patients using these methods. Next generation sequencing (NGS) is a promising tool that can improve soft-tissue sarcoma diagnosis.
Methods
A novel sarcoma-specific NGS gene capture panel containing probes for 90 fusion genes and 7 genes with frequent copy number changes was designed, optimised and validated in order to improve fusion-positive sarcoma diagnosis. Genomic DNA was extracted from 92 well-characterised FFPE samples and libraries prepared using the KAPA Hyperplus kit (Roche) and hybridised using the SeqCap Hybridisation kit (Roche) and sequenced on a NextSeq platform (Illumina).
Results
Sarcoma specific translocations or gene amplifications were identified in 92 out of 94 cases giving the targeted gene panel a sensitivity of approximately 98% and specificity of 100% (Table).Table:
1717P Sarcoma tumour types and number of cases with structural variants or copy number variations detected
Soft Tissue Tumour Type | No. of cases | SV/CNV detected |
---|---|---|
Synovial Sarcoma | 25 | 25 |
Alveolar Rhabdomyosarcoma | 6 | 6 |
Well/Dedifferentiated Liposarcoma | 9 | 8 |
Intimal Sarcoma | 1 | 1 |
Desmoplastic Small Round Cell Tumour (DSRCT) | 2 | 2 |
Ewing’s Sarcoma | 11 | 11 |
Inflammatory Myofibroblastic Tumour | 2 | 2 |
Myxoid Liposarcoma | 10 | 10 |
Chondroid Lipoma | 1 | 1 |
Clear Cell Sarcoma | 4 | 4 |
Epithelioid Haemangioendothelioma | 2 | 1 |
Low-grade Fibromyxoid Sarcoma | 3 | 3 |
Nodular Fasciitis | 1 | 1 |
Alveolar Soft Part Cell Sarcoma | 1 | 1 |
Congenital Fibrosarcoma | 2 | 2 |
Solitary Fibrous Tumour | 2 | 2 |
Aneurysmal Bone Cyst | 1 | 1 |
BCOR-CCNB3 Sarcoma | 1 | 1 |
Extraskeletal Myxoid Chondrosarcoma | 5 | 5 |
Mesenchymal Chondrosarcoma | 2 | 2 |
Dermatofibrosarcoma Protuberans (DFSP) | 3 | 3 |
TOTAL | 94 | 92 |
Conclusions
To the best of our knowledge this is the first sarcoma-specific NGS panel validated in FFPE-derived genomic DNA. It is at least as sensitive and specific as the combination of FISH and RT-PCR and can be implemented in routine clinical diagnostic workflows. We are currently investigating whether fusion genes can be detected in plasma using ctDNA from 14 patients and results will be reported at the conference.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
David Gonzalez de Castro.
Funding
Sarcoma UK.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract
4294 - The Patient Voice: An Irish Survey of Nutrition Attitudes & Access to Dietetic Care Throughout the Cancer Journey
Presenter: Erin Stella Sullivan
Session: Poster Display session 1
Resources:
Abstract
1925 - Homcology: home chemotherapy delivery in a simultaneous care project for frail advanced cancer patients
Presenter: Claudio Chini
Session: Poster Display session 1
Resources:
Abstract
4701 - Treatment-related adverse events and tolerability in patients with advanced non-squamous non-small cell lung cancer treated with first-line checkpoint inhibitors in combination with chemotherapy
Presenter: Ruth D'cunha
Session: Poster Display session 1
Resources:
Abstract
2985 - Clinical utility of a systematic toxicity assessment form (STAF) in patients with breast cancer receiving adjuvant or neoadjuvant therapy.
Presenter: Jwa Hoon Kim
Session: Poster Display session 1
Resources:
Abstract
2358 - Physicians’ satisfaction with Health-related quality of life (HRQoL) assessment in daily clinical practice using electronic patient-reported outcome (ePRO) for cancer patients.
Presenter: Guillaume Mouillet
Session: Poster Display session 1
Resources:
Abstract
5172 - Predictors of Survival in Patients with Incurable Cancer
Presenter: Erin Stella Sullivan
Session: Poster Display session 1
Resources:
Abstract
2281 - Patients and Physicians' Satisfaction with Telemedicine (TM) in Cancer Care and Factors that Correlate with a Positive Patient’s Experience
Presenter: Hurria Gondal
Session: Poster Display session 1
Resources:
Abstract
2193 - Adherence to ESMO 2014 guidelines on bone-targeting agent (BTA) initiation for breast and prostate cancer patients: real-world insights from practicing European physicians
Presenter: Alex Rider
Session: Poster Display session 1
Resources:
Abstract
2200 - Use of skeletal-related events preventive agents in patients with solid tumours and bone metastases in central Denmark
Presenter: Anders Boysen
Session: Poster Display session 1
Resources:
Abstract