Abstract 1966P
Background
Gene fusion is an increasingly important genomic aberrant in cancer diagnosis and treatment. Panel based RNAseq is particularly useful in detecting gene fusion since it avoids the intricate probe design for gene rearrangement at the DNA level. In this study, we studied gene fusion in a cohort consisting of mainly soft tissue sarcomas by an integrative DNA and RNA panel.
Methods
Formalin fixed and parafiin embedded (FFPE) tumor samples and matched blood of 173 Chinese patients were collected for next-generation sequencing (NGS)-based 450 genes DNA and RNA panel assay at OrigiMed, a College of American Pathologists accredited and Clinical Laboratory Improvement Amendments certified laboratory.
Results
The cohort contained samples from a total of 173 cancer with a median age of 33 years (range from 3 to 71 years) including 91 male (median age=30 years) and 82 female (median age=38 years). Most of the tumors are soft tissue sarcomas including ewing sarcoma (N=27, 15.61%), synovial sarcoma (N=27, 15.61%), rhabdomyosarcoma (N=12, 6.94%), liposarcoma (N=11, 6.36%) and other types with less than 10 cases. Among the 173 well characterized gene fusions detected by the integrative panel, 127 events (73.41%) were detected by both DNA and RNA panels, 33 gene fusions (19.08%) were detected by RNASeq, and 13 gene fusions (7.51%) were detected by DNA panel. The recurrent gene fusion events detected both at the DNA and RNA levels were SS18 (e9)-SSX1 (e6), ASPSCR1 (e7)-TFE3 (e6), EWSR1 (e7)-FLI1 (e6), LMNA (e2)-NTRK1 (e11), NAB2 (e6)-STAT6 (e16), FUS (e5)-DDIT3 (e2) and so on. The gene fusion detected by RNA panel including BCOR (e15)-CCNB3 (e5), PAX3 (e7)-FOXO1 (e2), MED12 (e43)-PRDM10 (e14), JAK3 (e23)-INSL3 (e2) and so on. Except for 7 samples with deteriorated RNA quality, the other 6 samples possessing gene fusion detected by DNA only were EWSR1 (e8)-FLI1 (e6), EWSR1 (e7)-ERG (e8), SS18 (e9)-SSX1 (e6), SS18 (e9)-SSX2 (e6), MYH9 (e1)-USP6 (e1) and MIR22HG (e1)-USP6 (e1). The absence of transcripts from these gene rearrangements may indicate the additional regulation on gene transcription.
Conclusions
Preliminary data from this small cohort of Chinese patient shows that integrative DNA and RNA sequencing improves the sensitivity of fusion gene detection.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Drum Tower Hospital Affiliated to Nanjing University medical school.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.