Key Points: An NUP98-PHF23 fusion collaborates with acquired Bcor and Jak/Stat mutations to produce a pro–B-1 ALL. Gene expression profile of murine pro–B-1 ALL resembles that of a subset of human ALL, suggesting some human ALLs arise from pro–B-1 B cells.

Epigenetic regulation of chromatin structure is a key determinant of transcriptional control and nuclear organization in cancer. Among histone lysine methyltransferases, SUV39H1 and SUV39H2 catalyze the trimethylation of histone H3 lysine 9 (H3K9me3), establishing repressive heterochromatin domains that are important for genomic stability. However, their pan-cancer expression dynamics, prognostic value, and structural implications remain poorly defined. In this study, we performed an integrative analysis of SUV39H1 and SUV39H2 across the Cancer Genome Atlas (TCGA) cohort to investigate their expression, prognostic relevance, associations with the immune landscape, and interactions with nuclear lamina genes. Both enzymes were significantly overexpressed in multiple tumor types, with SUV39H2 showing particularly high expression in high-grade serous ovarian cancer (HGSOC), where elevated levels correlated with poor overall survival (HR = 3.27, p < 0.001). Immune infiltration analysis revealed that high SUV39H2 expression was inversely associated with tumor-infiltrating lymphocytes, indicating reduced immune infiltration. Correlation studies demonstrated strong positive associations between SUV39H1/H2 and Lamin B genes (LMNB1, LMNB2), suggesting an association with nuclear lamina–linked heterochromatin. Conversely, Lamin A (LMNA) exhibited weak or negative correlation with SUV39 enzymes. Functional validation in A2780 ovarian cancer cells demonstrated that pharmacological inhibition of SUV39H2 by Chaetocin resulted in the upregulation of Lamin A, suggesting that SUV39H1/H2 inhibition is associated with Lamin A regulation. Collectively, our findings uncover a previously underappreciated association between SUV39H2, chromatin–lamina interactions, and immune evasion in ovarian cancer, highlighting SUV39H2 as a potential chromatin-associated biomarker and regulator of nuclear organization and providing a rationale for targeting SUV39H2 in therapeutic epigenetic interventions.

Epigenetic regulation of chromatin structure is a key determinant of transcriptional control and nuclear organization in cancer. Among histone lysine methyltransferases, SUV39H1 and SUV39H2 catalyze the trimethylation of histone H3 lysine 9 (H3K9me3), establishing repressive heterochromatin domains that are essential for genomic stability. However, their pan-cancer expression dynamics, prognostic value, and structural implications remain poorly defined. In this study, we performed an integrative analysis of SUV39H1 and SUV39H2 across the Cancer Genome Atlas (TCGA) cohort to investigate their expression, prognostic relevance, associations with the immune landscape, and interactions with nuclear lamina genes. Both enzymes were significantly overexpressed in multiple tumor types, with SUV39H2 showing particularly high expression in high-grade serous ovarian cancer (HGSOC), where elevated levels correlated with poor overall survival (HR = 3.27, p < 0.001). Immune infiltration analysis revealed that high SUV39H2 expression was inversely associated with tumor-infiltrating lymphocytes, indicating an immunosuppressive tumor microenvironment. Correlation studies demonstrated strong positive associations between SUV39H1/H2 and Lamin B genes (LMNB1, LMNB2), implicating their role in maintaining nuclear architecture and heterochromatin tethering. Conversely, Lamin A (LMNA) exhibited weak or negative correlation with SUV39 enzymes. Functional validation in A2780 ovarian cancer cells demonstrated that pharmacological inhibition of SUV39H2 by Chaetocin resulted in the upregulation of Lamin A, indicating epigenetic repression of LMNA by SUV39H2. Collectively, our findings uncover a novel link between SUV39H2, chromatin–lamina interactions, and immune evasion in ovarian cancer, providing a rationale for targeting SUV39H2 in therapeutic epigenetic interventions.

Background: Ovarian cancer (OC) is the most prevalent gynecological malignancy in women, often diagnosed at an advanced stage due to the absence of specific clinical biomarkers. Notch signaling, particularly Notch3, is frequently activated in OC and contributes to its oncogenic role. Despite its known association with poor clinical outcomes, the biomarker potential of Notch3 remains inadequately explored. Methods: We investigated the biomarker potential of Notch3 in OC using multiple databases, including ONCOMINE, GEPIA, Human Protein Atlas, UALCAN, Kaplan–Meier Plotter, and LinkedOmics. We analyzed Notch3 expression levels, survival correlations, and clinicopathological parameters. Results: Notch3 expression was significantly upregulated in OC, as well as other cancers. Correlation analysis demonstrated that high Notch3 mRNA levels were associated with poor overall survival (OS) (p < 0.05) and relapse-free survival (p < 0.05) in OC patients. Human Protein Atlas data showed elevated Notch3 protein levels in OC tissues compared to healthy controls. Clinicopathological analysis indicated significant associations between Notch3 expression and patient age (p < 0.5), TP53 mutation status (p < 0.5), and cancer stage (p < 0.1). Additionally, genes such as WIZ, TET1, and CHD4 were found to be co-expressed with Notch3 in OC. Notch3 expression also correlated with immune cell infiltration in OC. Conclusions: Our bioinformatics analysis highlights Notch3 as a potential biomarker for poor prognosis in OC. However, further in vitro and in vivo studies, along with validation using larger tissue samples, are necessary to confirm its biomarker utility.