GET3 – Prostate Cancer

GET3 (HGNC:752) has been observed in integrated genomic analyses of prostate cancer (MONDO_0008315), where it was included among a panel of genes altered in multisampled metastatic tumors (PMID:27148588). Although its recurrence in these studies suggests a potential role in prostate tumorigenesis, the case-level evidence remains sparse and indirect.

The overall clinical validity of the GET3–prostate cancer association is best classified as Limited. There is an absence of detailed segregation data or independent case reports that specifically implicate GET3 variants in prostate cancer, and the clustered genomic findings do not provide a clear genotype–phenotype correlation (PMID:27148588).

Genetic evidence is limited. Although a variant, c.488T>C (p.Val163Ala), has been reported in GET3, it originates from studies in a different clinical context (pediatric cardiomyopathy) and hence does not contribute direct case‐level support for its role in prostate cancer (PMID:31461301). No prostate cancer‐specific case reports have highlighted additional variant classes or segregation patterns in affected families.

Functional evidence for GET3 is also limited. Experimental studies in yeast have demonstrated that GET3 plays an important role in membrane-associated protein regulation (PMID:16816426), while analyses in cardiomyopathy models confirm its impact on protein targeting (PMID:31461301). However, these functional assessments have not been directly extended to prostate tissue or tumor biology, leaving its mechanistic contribution to prostate carcinogenesis unresolved.

In summary, while GET3 has been identified through broad genomic screens in metastatic prostate cancer, the absence of direct case-level genetic evidence and prostate-specific functional data limits its current clinical utility. Further targeted studies are needed to elucidate the exact role of GET3 and to validate its pathogenic mechanism in prostate cancer.

Key take‑home sentence: GET3’s inclusion in prostate cancer genomic analyses highlights its potential involvement in tumor biology, but current evidence remains too limited for immediate clinical application.

References

• Cold Spring Harbor molecular case studies • 2016 • Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer PMID:27148588
• Genetics • 2006 • The conserved ATPase Get3/Arr4 modulates the activity of membrane-associated proteins in Saccharomyces cerevisiae PMID:16816426
• Circulation. Genomic and precision medicine • 2019 • Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy PMID:31461301

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