American Association for Cancer Research
Browse
- No file added yet -

Table S3 from The Oncogenic FOXL2 C134W Mutation Is a Key Driver of Granulosa Cell Tumors

Download (50.66 kB)
dataset
posted on 2023-03-31, 06:02 authored by Elena Llano, Anne Laure Todeschini, Natalia Felipe-Medina, María D. Corte-Torres, Yazmine B. Condezo, Manuel Sanchez-Martin, Sara López-Tamargo, Aurora Astudillo, Xose S. Puente, Alberto M. Pendas, Reiner A. Veitia

Suppl table 3

Funding

Ministerio de Ciencia e Innovación (MICINN)

Junta de Castilla y León (JCYL)

Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA)

History

ARTICLE ABSTRACT

Adult-type granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex cord–stromal tumors. Most AGCTs carry the somatic variant c.402C>G (p.C134W) affecting the transcription factor FOXL2. Germline dominant variants in FOXL2 are responsible for blepharophimosis syndrome, which is characterized by underdevelopment of the eyelid. In this work, we generated a mouse model harboring the C134W variant of FOXL2 to evaluate in vivo the poorly understood oncogenic role of FOXL2. The mutation was dominant regarding eyelid hypoplasia, reminiscent of blepharophimosis syndrome. Interestingly, Foxl2+/C134W female mice had reduced fertility and developed AGCTs through a progression from abnormal ovaries with aberrant granulosa cells to ovaries with stromal hyperplasia and atypia and on to tumors in adut mice. The genes dysregulated in mouse AGCTs exhibited the hallmarks of cancer and were consistent with a gain-of-function of the mutated allele affecting TGFβ signaling. A comparison of these data with previous results on human AGCTs indicated similar deregulated pathways. Finally, a mutational analysis of mouse AGCT transcriptomic data suggested the absence of additional driver mutations apart from FOXL2-C134W. These results provide a clear in vivo example in which a single mutational hit triggers tumor development associated with profound transcriptomic alterations. A newly generated mouse model carrying a FOXL2 mutation characteristic of adult-type granulosa cell tumors shows that FOXL2 C134W shifts the transcriptome towards a signature of granulosa cell cancer and drives tumorigenesis.

Usage metrics

    Cancer Research

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC