Abstract 1658P
Background
NTRK gene fusions resulting in the elevated expression of TRK kinases were discovered in a wide variety of tumor types but generally at a low frequency. FDA approved TRK inhibitors such as larotrectinib and entrectinib in patients with TRK fusion positive cancers, regardless of age or the tumor type.
Methods
Formalin Fixed Paraffin Embedded (FFPE) samples of 599 Chinese sarcoma patients were collected from nearly 58 kinds of subtype of sarcoma for next-generation sequencing (NGS) assay with 638-gene panel. The testing was carried out by OrigiMed, a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China.
Results
We analyzed 170 children (age≤19 years) and 429 adults (age＞19 years). 24 patients were identified as NTRK fusion positive, with 12 children and 12 adults, which accounted to approximately 4.1% of the Chinese sarcoma patients in our cohort. NTRK fusions were found in 7.1% of children, including rhabdomyosarcoma (3%) and fibrosarcoma (50%), and 2.8% in adults, including rhabdomyosarcoma (14.3%), synovial sarcoma (3.7%), undifferentiated pleomorphic sarcoma (3.5%) and osteosarcoma (3.4%). 13 out of 24 patients harbored NTRK1 fusions, 2 with NTRK2 fusions, and the remained ones were NTRK3 fusions with 9 partners. LMNA (8/24), ETV6 (4/24), TPM3 (2/24) were the most common partners of NTRK fusion in this cohort. Moreover, we identified uncommon partner genes by NGS, including CHTOP, SLC28A3, LOXL1, LRRC28, ZNF704, SH2D2A and TPR. Based on the NGS results, several actionable genomic alterations including CDKN2A, BRCA2, and CDK4 were found in this study. We also found 10 patients harbored NTRK amplification in our cohort, who may also benefit from TRK kinases.
Conclusions
Our study revealed NTRK fuisons in approximately 7.1% and 2.8% in children and adults of Chinese sarcoma patients, respectively. Ten different partners of NTRK fusion were identified by NGS, NTRK fusions were found in more than nine types of sarcoma. NGS panel sequencing showed the advantage of detecting NTRK fusion and providing structure information of partners which could potentially guide more precise treatment options.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Yao, X. Dong, L. Qian, Y. Qu: Full/Part-time employment: OrigiMed. All other authors have declared no conflicts of interest.