TBRG4 and Plasma Cell Myeloma

The association between TBRG4 and plasma cell myeloma is supported by multiple lines of evidence from multi‐patient genomic studies. In one study, gene expression profiling of extramedullary relapse samples (9 EM and 9 BM plasma cell samples (PMID:25877407)) identified significant deregulation of TBRG4 among a panel of high‑risk genes. This finding emphasizes the potential clinical relevance of TBRG4 expression in the aggressive phenotype of plasma cell myeloma.

Genetic evidence stems from an extensive eQTL study where 1327 multiple myeloma cases were genotyped and subsequent replication was performed in an additional 1277 cases (PMID:33675538). These analyses revealed that specific TBRG4 polymorphisms are significantly associated with overall survival. Although no classical HGVS coding variant was reported, the robust eQTL associations support the gene’s prognostic impact in the disease.

While detailed segregation analysis was not performed in these studies, the large sample sizes and replicated associations across independent cohorts provide a compelling genetic signal. The association does not follow a simple Mendelian inheritance pattern but rather a complex trait architecture that underlies risk in plasma cell myeloma.

Functional assessments, though limited, have demonstrated differential expression of TBRG4 in high‑risk myeloma subtypes. Preliminary functional studies reported changes consistent with its role in gene regulation; however, further experimental work is needed to elucidate the precise mechanism of pathogenicity. This suggests that while TBRG4 may contribute to disease progression, its mechanistic role remains to be firmly established.

In summary, the integration of genetic association data with preliminary functional insights supports a strong link between TBRG4 and plasma cell myeloma. Additional evidence beyond the ClinGen scoring maximum is emerging, further substantiating its clinical utility.

Key Take‑home: TBRG4 represents a promising biomarker for identifying high‑risk plasma cell myeloma and may guide therapeutic stratification in clinical practice.

References

• Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia • 2015 • Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data PMID:25877407
• International journal of cancer • 2021 • Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients PMID:33675538

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