INPP5J and Breast Cancer

This summary evaluates the association between INPP5J (HGNC:8956) and breast cancer (MONDO_0007254) as presented in a familial cancer study. In the reported case, exome sequencing and SNP genotyping of two affected siblings revealed extensive regions of homozygosity in which several candidate genes—including INPP5J—were identified (PMID:27900359). Although the study highlighted five genes from these regions, only CHEK2 was supported by direct functional assays, while INPP5J was implicated solely through its positional candidacy. There was no specific INPP5J variant reported that fulfilled the ClinGen criteria (i.e. a complete coding change with both c. and (p…) descriptions), and no follow‐up segregation or experimental analysis was provided for INPP5J. Consequently, the genetic evidence for INPP5J remains limited given that only a candidate association is observed in a small familial cohort (2 probands (PMID:27900359)) without additional independent replication or definitive variant data. Similarly, functional studies focused on the pathogenicity of the CHEK2 mutation, leaving the mechanistic basis of INPP5J involvement in breast cancer unsubstantiated. Overall, while INPP5J emerges as a plausible candidate from genomic screening in the context of autosomal recessive predisposition, the current evidence does not suffice to elevate its clinical validity beyond a limited classification.

Key take‑home message: Further targeted studies, including direct mutation analysis and functional assays, are required before INPP5J can be reliably utilized for diagnostic or commercial applications in breast cancer.

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)