INPP5J – Prostate Cancer

This summary evaluates the association between INPP5J (HGNC:8956) and prostate cancer (MONDO_0008315) as reported in a single familial study. In the reported case, affected individuals presented with a spectrum of malignancies including prostate cancer, prompting a multi‐gene analysis that identified homozygous regions covering several candidate genes, among which INPP5J was incidentally noted (PMID:27900359).

The overall clinical validity for the INPP5J–prostate cancer association is assessed as Limited. This classification is based on evidence derived from a single familial study comprising 2 probands (PMID:27900359). Although the familial analysis included homozygosity testing and a candidate gene approach across multiple cancers, the lack of additional unrelated probands and replication studies limits the strength of the evidence.

Genetic evidence supports an autosomal recessive inheritance pattern, consistent with the observation of large regions of homozygosity in the affected siblings. However, only 2 probands were reported and no further affected relatives with segregating INPP5J variants were noted (PMID:27900359). This paucity of data restricts the ability to robustly assign causality to INPP5J alone.

No specific INPP5J variant was documented in the mutation list from the study. As such, the variant spectrum for INPP5J remains undefined in the current report, and this gap further undermines the genetic evidence supporting the association.

Functional assessment studies in the same report primarily evaluated a co‐investigated gene (CHEK2). No direct functional assays, animal models, or rescue experiments were performed to elucidate how alterations in INPP5J might contribute to prostate cancer pathogenesis (PMID:27900359). Therefore, functional evidence for INPP5J remains limited.

In summary, while INPP5J has been identified in the context of a familial cancer syndrome that includes prostate cancer, the evidence remains preliminary. The genetic findings are currently confined to a single familial report with limited segregation data and no direct functional validation. Additional studies, including further case reports and experimental investigations, are needed to clarify the role of INPP5J in prostate cancer predisposition.

Key Take‑home: Although INPP5J appears as a candidate in familial cancer studies, its association with prostate cancer requires further validation before it can inform routine clinical diagnostic or therapeutic decision‑making.

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

Evidence Based Scoring (AI generated)