SPEN mutation

Our findings expand knowledge on their clinical and molecular features. We present the first molecular profile of primary CNS intraparenchymal EMZL, underscoring the need for further research to understand their biology and optimize treatment strategies.

Immunohistochemistry showed varying degrees of positivity for intestinal markers in our patients. In one patient, we identified a deletion involving chromosome 18q in a region previously described as characteristic of small intestinal neuroendocrine tumours. These findings indicate intestinal differentiation and a possible relationship between these tumours and small intestinal neuroendocrine tumours.

Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM.

We conclude that SPEN mutations might improve ICI efficacy in CRC due to increased immunogenicity and an inflammatory tumor microenvironment. SPEN mutations could be predictive biomarkers for ICI responsiveness, underscoring their value in personalized therapy and highlighting the importance of genomic data in clinical decisions. This research lays the groundwork for future precision oncology studies.

SPEN loss-of-function is associated with tamoxifen resistance in preclinical models... SPEN mutations were detected mostly in patients with HR+/HER2- MBC and at a higher frequency than reported in primary disease via TCGA. SNVs were common, though it remains unclear whether these comprise driver versus passenger mutations. While no mutational hotspots were identified, several novel loss-of-function truncating mutations were identified, which warrant further validation of functional and clinical significance.

WES identified 29/404 ndDLBCL (7.2%) harboring SPEN mutations; n=17 missense and n=12 nonsense or frameshift insertions/deletions (truncating variants - [trunc]), the later considered as the focal point of our study. Against all cases, SPEN trunc cases displayed enrichment for high-risk factors including non-GCB COO (p=0.06, OR=3.7, 95% CI [0.9, 22.2]) and primary refractory disease (PTR; p=0.02, OR=5.0, 95% CI [1.05, 19.9]), and demonstrated inferior OS (p=0.06, HR=2.2), where a majority of clinical progression events occurred within 12 months of diagnosis. Leveraging RNA-seq, we observed 11 of 11 SPEN trunc cases exhibiting a double-hit negative gene expression signature, 9/11 cases with inflammatory or depleted microenvironment (LME), and 8/11 with a signature associating with intermediate/high risk of EFS24 failure.

Conclusion Our multi-dimensional profiling approach enabled us to delineate molecular profiles of HRS cells that are linked to distinct TME patterns. These linkages have implications for current pathogenesis models, molecular subtyping of CHL, and identification of cellular vulnerabilities that might be therapeutically exploitable via targeting of HRS cell phenotypes and/or immune escape mechanisms.

Survival analysis suggests that SPEN mutation may serve as a novel predictive biomarker in GC patients with ICIs, but not a prognostic factor. The significantly higher CD8+ T cell infiltration and activated CD4 memory T cell in SPEN-mutant group may be the potential mechanism.

The aaIPI staging combination with molecular biology markers is more conducive to accurately judging the prognosis of young DLBCL patients. TP53, POU2AF1 and CCND3 mutations predict worse survival in the patients with the aaIPI high-risk group.