Characterizing the genomic landscape through the lens of FOLR1 status in low and high grade serous ovarian carcinoma.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0365304 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-6859 (Electronic) Linking ISSN: 00908258 NLM ISO Abbreviation: Gynecol Oncol Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Ovarian Neoplasms*/genetics ; Ovarian Neoplasms*/pathology ; Ovarian Neoplasms*/metabolism ; Folate Receptor 1*/genetics ; Folate Receptor 1*/metabolism ; Cystadenocarcinoma, Serous*/genetics ; Cystadenocarcinoma, Serous*/pathology ; Cystadenocarcinoma, Serous*/metabolism ; Neoplasm Grading*; Humans ; Female ; Middle Aged ; Proto-Oncogene Proteins p21(ras)/genetics ; Mutation ; Proto-Oncogene Proteins B-raf/genetics ; GTP Phosphohydrolases/genetics ; Aged ; Membrane Proteins/genetics ; High-Throughput Nucleotide Sequencing ; B7-H1 Antigen
    • Abstract:
      Objective: Targeted therapy in folate receptor alpha (FOLR1)-positive high grade serous ovarian carcinoma (HGSOC) is now a mainstay for platinum-resistant disease. However, the rate of FOLR1-positivity in low grade serous ovarian carcinoma (LGSOC) is not well documented. Less common than HGSOC, LGSOC tends to respond poorly to traditional platinum-based chemotherapeutic regimens, particularly in recurrence. Thus, there is an urgent need to identify molecular targets that may assist in identifying more efficacious treatments for LGSOC. In this work, we assessed the genomic and transcriptomic landscapes in FOLR1-positive/negative LGSOC compared to its high-grade counterpart.
      Methods: Using a large precision oncology database, next-generation sequencing and immunohistochemistry was performed on a cohort of 281 LGSOC and 5086 HGSOC. Associated MAPK activation was calculated based on NGS results and patient survival analysis was completed stratified by molecular alteration.
      Results: Compared with LGSOC (24.6 %), HGSOC tumors have significantly higher prevalence of FOLR1+ status (43.5 %) and significantly higher PD-L1+ status. Conversely, LGSOC had higher prevalence of KRAS and NRAS mutations, with a near exclusivity for BRAF mutation compared to HGSOC. FOLR1- LGSOC and HGSOC had similar prevalences of T cell-inflamed tumors, though FOLR1+ LGSOC had a significantly lower prevalence of T-Cell inflamed tumors than FOLR1+ HGSOC. MAPK activation, quantified via MAPK activation score (MPAS), was significantly higher in low-grade tumors compared to HGSOC, yet no difference between FOLR1+ vs FOLR1- LGSOC was observed.
      Conclusions: Though less than in high-grade disease, a notable portion of low-grade tumors were FOLR1+, suggesting FOLR1 expression in LGSOC could be a viable target for this rare histology, particularly in the recurrent setting.
      Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: FOLR1; Molecular oncology; Molecular profiling; Ovarian carcinoma
    • Accession Number:
      0 (Folate Receptor 1)
      0 (FOLR1 protein, human)
      EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
      0 (KRAS protein, human)
      EC 3.6.1.- (NRAS protein, human)
      EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
      EC 3.6.1.- (GTP Phosphohydrolases)
      EC 2.7.11.1 (BRAF protein, human)
      0 (Membrane Proteins)
      0 (CD274 protein, human)
      0 (B7-H1 Antigen)
    • Publication Date:
      Date Created: 20241004 Date Completed: 20241212 Latest Revision: 20241212
    • Publication Date:
      20241213
    • Accession Number:
      10.1016/j.ygyno.2024.09.021
    • Accession Number:
      39366033