Refractory and metastatic infantile fibrosarcoma harboring LMNA-NTRK1 fusion shows complete and durable response to crizotinib.
Jonathan BenderBailey AndersonDavid A BloomRaja RabahRhonda McDougallPankaj VatsRajen ModyPublished in: Cold Spring Harbor molecular case studies (2019)
Infantile fibrosarcoma (IFS) is a rare soft-tissue sarcoma, which classically presents as an aggressive and rapidly enlarging tumor over the distal extremities of children in their first year of life. The presence of ETV6 and NTRK3 gene rearrangement is characteristic of IFS, which can be detected on routine fluorescence in situ hybridization (FISH) testing. Patients with IFS typically respond well to surgical resection and chemotherapy and have an overall survival of ∼90%. In this report, we outline the use of integrative clinical sequencing (ICS) including RNA-seq in a patient with refractory, metastatic IFS to reveal an unusual fusion (LMNA-NTRK1), not detected by routine FISH testing, which was treated with oral crizotinib and resulted in a complete and durable long-term response. This study highlights the utility of ICS in identifying cryptic gene fusions, especially in refractory malignancies, and demonstrates how such information can be used to select targeted therapies in patients with actionable molecular alterations.
Keyphrases
- rna seq
- single cell
- genome wide
- squamous cell carcinoma
- small cell lung cancer
- copy number
- clinical practice
- advanced non small cell lung cancer
- single molecule
- genome wide identification
- young adults
- acute lymphoblastic leukemia
- muscular dystrophy
- case report
- healthcare
- dna methylation
- minimally invasive
- transcription factor
- free survival
- network analysis
- gene expression
- soft tissue
- energy transfer
- duchenne muscular dystrophy