HRD

The HGOC HRD-GIS determined by the MyChoice HRD+ CDx assay provides statistically robust evidence for BRCA1 and BRCA2 variant interpretation. This approach may refine variant classification, particularly for variants of uncertain significance, and enhance clinical decision-making in hereditary and tumor-based cancer risk assessment.

Integration of RNA expression data revealed RAD51D , but not XRCC2 , is exceptionally sensitive to splice-altering variation, with 24% of RAD51D loss-of-function missense variants acting through RNA-mediated mechanisms compared to only 5% in XRCC2 . These SGE datasets provide strong, splice-resolved functional evidence to support variant classification across both genes.

Although HBOC-related genetic testing and preventive strategies are widely implemented in Japan, this nationwide survey revealed critical structural and evidence gaps, particularly in institutional capacity and the management of evidence-limited scenarios such as STIC, underscoring the need for system-level improvement.

These findings support the investigation of rational combination approaches informed by sensitive detection methods and functional testing to address resistance in ultra-rare cancers. Implications: Integrative multi-omic profiling combined with functional testing in DSRCT reveals patient-specific vulnerabilities and biologically targetable receptor and DNA damage response dependencies, while defining immune states that may inform therapeutic response and rational combination strategies in this rare, fusion-driven cancer.

As these genes have extra-P-body functions, the score serves as a transcriptomic proxy for P-body component enrichment, not a direct measure of P-body activity. Despite this limitation, it offers a clinically useful tool for risk stratification and mechanistic hypotheses.

BRCA-associated pancreatic ductal adenocarcinomas demonstrate recurrent morphologic patterns, including increased glandularity, stromal hyalinization, myxoid stromal change and architectural heterogeneity. These observations provide a framework for future comparative studies investigating morphologic correlates of homologous recombination deficiency in pancreatic cancer. Recognition of these patterns may support consideration of germline or somatic DNA-repair gene testing in appropriate clinical settings.

P2, N=30, Not yet recruiting, Danatlas Pharmaceuticals Co., Ltd

P2, N=120, Not yet recruiting, Shandong University

Due to limited germline and epigenetic data, MSI-H tumors could not be classified as Lynch-associated or sporadic. Overall, MSI-H and MSS CRCs in the Chinese population demonstrate distinct molecular landscapes in terms of TMB, HRD, EBV status, and driver gene alterations, underscoring the molecular heterogeneity of MSI-H CRC and the need for future studies integrating germline and epigenetic data to refine subtype classification.

One patient had a single brain metastasis and received comprehensive treatment including surgery, radiotherapy, chemotherapy, PD-1 inhibitor (tislelizumab), and PARP inhibitor (niraparib). The immune microenvironment characteristics of brain metastases (e.g., high PD-L1 expression, T-cell infiltration) may predict the efficacy of immunotherapy, but the prognosis for patients with multiple brain metastases remains poor. Further research is needed to explore the correlation between peripheral blood immune markers and treatment response in brain metastases.

In patients demonstrating substantial response to neoadjuvant chemotherapy (CRS 2-3), PARPi maintenance was associated with improved PFS, whereas no benefit was observed for CRS 1. The score may aid counseling regarding PARPi initiation, particularly in BRCA-wildtype patients or where homologous recombination deficiency (HRD) testing access is limited.

Since the initial US Food Administration approval of olaparib in 2014, PARP inhibitors have shown efficacy across ovarian, breast, and prostate cancers, although differences in trial design and biomarker strategies have resulted in tumor-specific indications...Ongoing studies are evaluating rational combinations targeting complementary DNA damage response pathways (ATR/CHK1/WEE1, PI3K/AKT) and integrating immunotherapy or hormonal agents to extend benefit. Moving forward, harmonizing HRD testing across tumor types, accounting for germline, somatic, and liquid biopsy-derived alterations, and refining patient selection will be essential to maximize therapeutic efficacy and safely expand PARP inhibitor use beyond canonical BRCA-mutated cancers.