CHCHD7 and Pleomorphic Adenoma

In pleomorphic adenoma, recurrent CHCHD7-PLAG1 fusion events have emerged as significant molecular signatures that support the association between CHCHD7 and this salivary gland tumor. A case report detailed a 57‑year‑old patient diagnosed with a hard palate tumor in which a CHCHD7‑PLAG1 fusion was identified, reinforcing the evidentiary link for CHCHD7 involvement (PMID:32702887). This isolated report provided initial molecular insights into the tumorigenesis of pleomorphic adenoma.

Subsequently, a multi‑patient study analyzing 105 pleomorphic adenoma cases reported that 14 cases harbored the CHCHD7‑PLAG1 fusion, among other fusion events detected with PLAG1. This replication in an independent patient cohort further reinforces the role of CHCHD7 alterations in these tumors (PMID:30307055). Although the total count of probands supporting this association is modest, the consistency of the CHCHD7‑PLAG1 fusion in separate studies strengthens the overall clinical validity.

Genetic evidence primarily derives from fusion gene detection. In the genetic assessment, 15 probands (one case report and 14 patients from a multi‑patient study) have been reported to bear CHCHD7‑PLAG1 fusions, which underlines its significance in the molecular profile of pleomorphic adenoma. While formal segregation studies are not available for this somatic event, the recurrent nature of the fusion in different clinical settings supports a moderate genetic contribution (PMID:32702887; PMID:30307055).

Functional studies that incorporate CHCHD7, although not directly performed in the context of pleomorphic adenoma, include assessments in cytochrome c oxidase biogenesis. One study demonstrated that a mutation in COX1 (I101F) could compensate for defects in other assembly factors, and CHCHD7 was listed among the genes of interest (PMID:28357365). However, direct in vitro or in vivo experiments confirming the functional impact of CHCHD7 alterations in pleomorphic adenoma remain limited.

Overall, the combined genetic and experimental evidence currently supports a moderate association between CHCHD7 and pleomorphic adenoma. The detection of recurrent CHCHD7‑PLAG1 fusion events across independent studies, despite the absence of extensive functional validation in the tumor context, lends confidence to the clinical utility of this biomarker. The available data underpin diagnostic refinements for pleomorphic adenoma and indicate potential avenues for commercial assay development and further research.

Key Take‑home sentence: The recurrent CHCHD7‑PLAG1 fusion is a promising molecular biomarker for pleomorphic adenoma that supports enhanced diagnostic precision and paves the way for targeted functional investigations.

References

• Medicine • 2020 • Molecular profile of a pleomorphic adenoma of the hard palate: A case report PMID:32702887
• Histopathology • 2019 • Clinicopathological effect of PLAG1 fusion genes in pleomorphic adenoma and carcinoma ex pleomorphic adenoma with special emphasis on histological features PMID:30307055
• Microbial Cell (Graz, Austria) • 2016 • Cox1 mutation abrogates need for Cox23 in cytochrome c oxidase biogenesis PMID:28357365

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