VGLL3

Overview

VGLL3 is a transcriptional co-activator that competes with YAP/TAZ for binding to TEAD transcription factors. In the corpus, VGLL3 shows recurrent focal copy-number gain in anaplastic thyroid carcinoma.

Alterations observed in the corpus

• VGLL3 exhibited a 429 kb focal gain on chromosome 3p in 18% of anaplastic thyroid carcinomas (ATCs) in a comprehensive genomic study (n=56 ATCs, n=67 PTCs) PMID:38412093.
• Focally amplified (11%) in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS); the VGLL3/YAP1 TEAD-cofactor target signature is strongly expressed (p=1e-24) in UPS/MFS, implicating Hippo pathway dysregulation as a driver in this histology spectrum PMID:29100075.

Cancer types (linked)

• THPA — focal 429 kb 3p gain in 18% of ATCs; not reported in PTCs or co-DTCs in this study PMID:38412093.
• USARC / MFS — focal amplification in 11% of UPS and MFS combined; VGLL3/YAP1 TEAD-cofactor target signature strongly expressed (p=1e-24), implicating Hippo pathway as a key driver in these histologies PMID:29100075.

Co-occurrence and mutual exclusivity

• VGLL3 gain co-occurs with other ATC CNA events (CDKN2A deletion, BRCA2 deletion, RB1 deletion) in the ATC genomic landscape PMID:38412093.

Therapeutic relevance

• No direct targeted therapy reported in the corpus; VGLL3 amplification implicates Hippo pathway-directed therapeutic strategies in UPS/MFS; emerging Hippo-pathway inhibitors are nominated PMID:29100075.

Open questions

• Whether VGLL3 gain drives Hippo pathway dysregulation in ATC and whether it is functionally distinct from YAP/TAZ amplification is not addressed in the corpus PMID:38412093.

Sources

• PMID:38412093
• PMID:29100075

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