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PR056/#319  High frequencies of fusion transcripts (FT) identified in ovarian clear cell carcinoma (OCCC) by comprehensive genomic profiling (CGP)
  1. Ruby Yun-Ju Huang1,
  2. Alice Hsiang-Kuo Yang2,
  3. Ko-Chen Chen1,
  4. Jung-Ming Jeng1 and
  5. Lin-Hung Wei1
  1. 1National Taiwan University College of Medicine, Taipei, Taiwan (China)
  2. 2National Taiwan University Hospital, Taipei, Taiwan (China)

Abstract

Introduction OCCC is a subtype of ovarian cancer with with high incidence in East Asia. OCCC tumors are known to have low frequencies of genomic alterations such as high tumor mutation burden (TMB), microsatellite instability (MSI), and high genomic instability scores (GIS). However, the molecular heterogeneity in FT has not been fully described.

Methods This study adopted a CGP approach using the Illumina TruSight Oncology 500 HRD assay to characterize a ten-year cohort of 160 early-stage OCCC tumors. DNA and RNA were extracted from FFPE tumors for library preparation. Libraries were sequenced on a NextSeq 550. Variant calling and analysis were performed using DRAGEN TSO 500 2.1.0.4 (with HRD).

Results Majority of tumors were TMB-low (133/160; 83.7%), microsatellite stable (MSS) (154/160; 96.3%), and GIS-low (157/160; 98.1%). High frequencies of FT (33/160; 20.6%) were identified with MET being the most frequent fusion loci (7/33; 21.2%) followed by FGFRs (5/33; 15.2%). Five tumors with MET FT (5/7, 71.4%) showed high immunoreactivity. Among 33 tumors with FT, all were MSS and GIS-low with 3 being TMB-high. Tumors without FT showed higher mean immune scores in CD45 (12.6% vs 7.7%, p= 0.005), CD8 (4.6% vs 2.6%, p= 0.027), and tryptase (2.7% vs 1.5%, p= 0.004). OCCC with FT had less recurrence (4/33, 12.1% vs 42/127, 33.1%). Among the detected FT, 8 were known and 21 were novel with CAPZA2::MET being the most common recurrent FT (5/160; 3.1%).

Conclusion/Implications Early-stage OCCC tumors showed high occurence of FT associated with lower immune scores and recurrence rate. Functional elucidation of novel FT is warranted.

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