GAB1-ABL1 fusions in tumors that have histologic overlap with NTRK-rearranged spindle cell tumors

Florence Choo, Dinesh Rakheja, Lara E. Davis, Monika Davare, Jason Y Park, Charles F. Timmons, Tanaya Neff, Carol Beadling, Christopher L. Corless, Jessica L. Davis

Research output: Contribution to journalArticlepeer-review

Abstract

Fibroblastic spindle cell tumors are a heterogeneous group of rare soft tissue tumors that are increasingly recognized as associated with a variety of kinase gene fusions. We report two cases of GAB1-ABL1 fusions in spindle cell tumors that histologically overlap with neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell tumors. The first case occurred in a 76-year-old female who had a large deep-seated spindle cell tumor composed of monotonous ovoid to spindle cells in a background of thick stromal collagen bands with prominent hyalinized vessels and inconspicuous mitoses (<1/10 HPF). Immunohistochemical stains showed co-expression of S100 and CD34. A GAB1-ABL1 fusion was detected by whole transcriptome RNA sequencing. The patient had a partial response to imatinib. The second case was previously described as a solitary fibrous tumor, occurring in a 9-year-old female with a cellular spindle cell tumor with patchy CD34 immunoexpression but no expression of S100. Upon clinicopathologic re-review, including anchored multiplex next-generation sequencing, a GAB1-ABL1 fusion was identified. In summary, we report the first two cases of spindle cell tumors with variable expression of CD34 and/or S100, driven by GAB1-ABL1 gene fusions with histologic overlap with NTRK-rearranged spindle cell tumors, suggesting that ABL-fusions may also be oncogenic drivers within this spectrum of tumors. These cases highlight the evolving understanding of fibroblastic spindle cell tumor biology and the utility of sequencing in identifying a targetable alteration.

Original languageEnglish (US)
Pages (from-to)623-630
Number of pages8
JournalGenes Chromosomes and Cancer
Volume60
Issue number9
DOIs
StateAccepted/In press - 2021

Keywords

  • ABL1
  • CD34
  • NTRK
  • S100
  • imatinib
  • sarcoma

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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