SOX17

Overview

SOX17 encodes a member of the SOX (SRY-related HMG-box) family of transcription factors. In endometrial cancer, SOX17 is recurrently mutated with novel missense variants and functions to mediate beta-catenin degradation, placing it in the WNT/beta-catenin signaling pathway. SOX17 mutations are mutually exclusive with CTNNB1 and KRAS mutations, consistent with its role in the same pathway.

Alterations observed in the corpus

  • SOX17 harbors recurrent novel missense mutations Ala96Gly and Ser403Ile in 8% of copy-number-low endometrial tumors; SOX17 mediates beta-catenin degradation and is mutually exclusive with CTNNB1 and KRAS mutations PMID:23636398

Cancer types (linked)

  • UCEC: SOX17 missense mutations occur in ~8% of copy-number-low MSS endometrioid endometrial carcinoma; mutually exclusive with CTNNB1 and KRAS PMID:23636398

Co-occurrence and mutual exclusivity

  • SOX17 mutations are mutually exclusive with CTNNB1 and KRAS mutations in endometrial cancer, consistent with convergent WNT/beta-catenin pathway activation PMID:23636398

Therapeutic relevance

  • SOX17 mutations implicate the WNT/beta-catenin pathway as a potential therapeutic target in copy-number-low endometrial cancers.

Open questions

  • The functional consequence of specific SOX17 missense variants (Ala96Gly, Ser403Ile) on beta-catenin degradation activity requires experimental validation.

Sources

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