PLAG1
Overview
PLAG1 (pleomorphic adenoma gene 1) encodes a zinc-finger transcription factor that is a known oncogene in pleomorphic adenoma and other tumors. It is a transcriptional target downstream of HMGA1 and HMGA2, and is upregulated in tumors with HMGA1/2 rearrangements including endometrial polyps, uterine leiomyomas, and lipomas.
Alterations observed in the corpus
- Transcriptional upregulation (downstream of HMGA1/2) in HMGA-rearranged endometrial polyps (WGS, 23 polyps): log2FC 3.22 in HMGA1-rearranged and 3.38 in HMGA2-rearranged polyps; no DNA-level alterations reported in PLAG1 itself in this cohort PMID:28445112.
Cancer types (linked)
- UCEC / ULM: PLAG1 overexpression is a transcriptional consequence of HMGA1/HMGA2 enhancer hijacking in endometrial polyps; previously identified as a HMGA1/HMGA2/PLAG1-leiomyoma biomarker PMID:28445112.
Co-occurrence and mutual exclusivity
- PLAG1 overexpression occurs downstream of HMGA1 (14/23 polyps) and HMGA2 (4/23 polyps) rearrangements; C19ORF38 is also upregulated in the same pathway context PMID:28445112.
Therapeutic relevance
- PLAG1 upregulation is a shared feature of endometrial polyps and uterine leiomyomas, suggesting any HMGA-targeted therapy (e.g., HMGA2 gene silencing explored in ovarian carcinoma) could in principle be repurposed across both lesion types PMID:28445112.
Open questions
- Whether PLAG1 transcriptional activation plays a functional driver role in endometrial polyp formation vs. being a secondary consequence of HMGA1/2 hijacking is not yet established PMID:28445112.
Sources
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