C19ORF38

Overview

C19ORF38 (chromosome 19 open reading frame 38) is a gene of uncertain function that has emerged as a transcriptional target downstream of HMGA1/HMGA2/PLAG1 signaling in mesenchymal neoplasms. It was originally reported as a biomarker for HMGA1/HMGA2/PLAG1-driven uterine leiomyomas, and has since been identified as one of the most upregulated genes in HMGA1/HMGA2-aberrant endometrial polyps, suggesting a shared transcriptional program across HMGA-driven uterine lesions.

Alterations observed in the corpus

  • C19ORF38 — ranked 13th most upregulated gene in HMGA1/HMGA2-aberrant endometrial polyps by 3′RNA-seq; no direct somatic DNA-level mutations reported; previously documented as a HMGA1/HMGA2/PLAG1-leiomyoma biomarker PMID:28445112

Cancer types (linked)

  • Endometrial polyps / ULM: C19ORF38 upregulation co-occurs with HMGA1/2 rearrangements in the stromal compartment of benign uterine lesions; the same expression signature was previously identified in uterine leiomyomas driven by HMGA1/HMGA2/PLAG1 PMID:28445112

Co-occurrence and mutual exclusivity

  • Transcriptional upregulation parallels that of ZMAT3 (the top upregulated gene), PLAG1, and other HMGA1/2 downstream targets in endometrial polyps with HMGA1 or HMGA2 chromosomal rearrangements PMID:28445112

Therapeutic relevance

  • No direct therapeutic targeting reported. Its upregulation may serve as a surrogate marker of HMGA1/HMGA2 pathway activation in uterine mesenchymal lesions PMID:28445112

Open questions

  • The function of C19ORF38 protein in normal and neoplastic uterine stroma is unknown; whether upregulation is a driver or a passenger of HMGA1/2 enhancer hijacking has not been determined PMID:28445112

Sources

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