SFI1 – Prostate Cancer

The association between SFI1 (HGNC:29064) and prostate cancer (MONDO_0008315) has been explored in candidate gene analyses derived from familial and multi‐patient studies. In one familial report, a cohort of patients with multiple primary cancers—including prostate cancer (PMID:27900359)—was evaluated by exome sequencing, and SFI1 was among the genes identified in runs of homozygosity. Although the primary focus of the report was on deleterious variants in CHEK2, the inclusion of SFI1 in the candidate panel suggests that its potential contribution to prostate cancer merits further scrutiny.

Genetic evidence for SFI1 is currently limited. In the studied family, while two siblings with a complex cancer phenotype (lung, breast, uterine, and prostate cancers) were documented (PMID:27900359), no specific pathogenic variant meeting stringent HGVS criteria for SFI1 was reported. Consequently, the segregation data for SFI1 remain minimal, and its role is inferred only indirectly from its co‐involvement in the candidate gene panel.

Functional studies provide moderate supporting evidence for SFI1’s biological relevance in oncogenesis. Experimental assessments in yeast models demonstrated that SFI1 is critical for proper spindle pole body duplication and separation, processes that are integral to cell cycle regulation (PMID:16972090; PMID:26779587). These findings suggest that perturbations in SFI1 function may contribute to tumorigenesis, although direct evidence in prostate tissue is not yet established.

The convergence of genetic and experimental findings supports a limited, albeit biologically plausible, role for SFI1 in the etiology of prostate cancer. The limited genetic evidence, characterized by the absence of SFI1‐specific variants and minimal segregation data, contrasts with the informative functional studies. This disparity underscores the current state of the evidence and highlights the need for additional investigations focusing directly on SFI1 in prostate cancer cohorts.

Despite these limitations, the integration of available familial case reports and functional assessments provides a coherent narrative. SFI1’s involvement in critical cell cycle processes and its inclusion in candidate gene panels offer a potential pathway through which it might influence prostate cancer risk. However, further studies with robust variant identification and comprehensive segregation analysis are essential to solidify this association.

Key take‑home: While current data suggest a potential role for SFI1 in prostate cancer pathogenesis, the clinical utility of this association hinges on future studies to validate and detail its genetic contribution.

References

• Cold Spring Harbor molecular case studies • 2016 • Homozygous inactivation of CHEK2 is linked to a familial case of multiple primary lung cancer with accompanying cancers in other organs PMID:27900359
• Current genetics • 2006 • Deletion of RNQ1 gene reveals novel functional relationship between divergently transcribed Bik1p/CLIP-170 and Sfi1p in spindle pole body separation PMID:16972090
• Biochimica et biophysica acta • 2016 • New insights into the interaction of centrin with Sfi1 PMID:26779587

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