Ankyrin G (ANK3), belonging to the ankyrin family, contributes to cellular structural integrity by linking the cytoskeleton to the plasma membrane. Abnormal ANK3 expression has been reported across several human malignancies, yet the regulatory mechanisms involved are still poorly understood. The process of dividing introns into several steps is referred to as recursive splicing (RS). RS can control the quality of transcripts produced by regulating the retention of the RS-exon. Hundreds of annotated RS-exons in human mRNAs are attributed to the inhibition of RS by the exon junction complex (EJC).

Primary liver cancer (PLC) exhibits a high incidence and mortality rate. Early diagnosis and effective treatment are crucial for improving patient survival rates. This study aims to identify biomarkers of hepatitis B-related liver cancer and establish a new method for molecular subtype classification based on differential metabolite-related regulatory gene expression profiles.

Resistance to anoikis is a critical mechanism that enables metastatic dissemination. Abrogation of this cellular safeguard is therefore a hallmark of aggressive cancer progression. Despite the importance of anoikis, there are still few biomarkers among anoikis-related genes (ARGs) that could aid in the prognostication of bladder cancer (BC) patients and potentially serve as drug targets.

Research on the molecular progression of esophageal squamous dysplasia to cancer remains limited. The majority of prior studies have focused on morphological precancerous lesions sampled adjacent to tumors, and have relied primarily on the analysis of data from whole-exome sequencing.

Clonal hematopoiesis (CH) is characterized by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations, which confers an increased risk of hematologic malignancies and cardiovascular disease. Among CH-associated mutations, mutations affecting splicing factors (SFs), including splicing factor 3b subunit 1 (SF3B1), serine/arginine-rich splicing factor 2 (SRSF2), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2 (ZRSR2), play a unique role in promoting clonal expansion and leukemogenesis. In this review, we summarize recent findings on the role of SF mutations in CH progression, their interplay with other mutations (e.g., DNA methyltransferase 3 alpha (DNMT3A), ten-eleven translocation methylcytosine dioxygenase 2 (TET2) and isocitrate dehydrogenase 2 (IDH2)), and their impact on hematopoietic homeostasis. Epidemiological studies have demonstrated that SF-mutant CH exhibits an accelerated clonal expansion compared to other CH clones. Furthermore, murine models suggest that SF mutations alone do not inherently confer a growth advantage for clonal expansion but rather enhance disease phenotypes when co-existing with epigenetic mutations, such as IDH2 and TET2. These findings suggest that SF mutations contribute to CH expansion and malignant transformation through a synergistic interplay with other mutations and external factors such as inflammation. Given the clinical significance of SF mutations, ongoing research is focused on developing targeted therapies that modulate aberrant RNA splicing and prevent CH-driven leukemogenesis. Understanding the mechanisms underlying mutant spliceosome-mediated CH expansion may provide novel insights into early detection, risk stratification, and therapeutic interventions in hematologic malignancies.

Pediatric high-grade gliomas (pHGGs) and diffuse midline gliomas (DMGs) represent some of the most aggressive and lethal childhood brain tumors. Recent molecular and epigenetic discoveries have redefined these entities as distinct from adult gliomas, with hallmark alterations such as H3K27M and H3G34R/V mutation driving unique biological behaviors. Advances in genomic, epigenomic, and transcriptomic profiling have enabled refined diagnostic classifications, improved our understanding of tumor heterogeneity, and revealed novel therapeutic targets. Despite these insights, standard of care approaches-primarily radiotherapy-remain palliative and conventional chemotherapy has shown limited efficacy. Emerging strategies, including targeted molecular therapies, immunotherapies, and innovative drug delivery techniques, offer promise but face significant challenges related to blood-brain barrier integrity, immune evasion, and intratumoral heterogeneity. Integration of DNA methylation profiling, enhancer landscape analysis, and liquid biopsy technologies are transforming diagnostic and monitoring capabilities. Future progress will depend on interdisciplinary collaboration, the development of predictive preclinical models, multi-omic integration, and adaptive clinical trial designs. Ultimately, tackling the biological complexity of pHGGs and DMGs through personalized, molecularly targeted approaches offers the best hope for improving outcomes in this devastating disease group.

Introduction Adamantinomatous craniopharyngioma (ACP) is a significant source of morbidity in the pediatric brain tumor population. It predominantly arises from the parasellar space. The tumors proximity to key vital structures often makes gross total surgical resection challenging and sometimes clinically inadvisable. Compounding the problem, adjunct therapies are not yet capable of providing a definitive cure. Recent preclinical research has made significant progress towards elucidating the mutagenic drivers of ACP, however much work remains to translate this into safe and effective treatments. Content Overview and Key Takeaways In the following chapter, we discuss the most up-to-date understanding of ACP biology and management. ACP is a histologically low grade tumor characterized by a mutation involving the beta-catenin protein, resulting in pathologic stability of the protein that impairs cell death or apoptosis. A subpopulation of tumor cells then enter a transcriptomic state characterized by cellular oncogenic senescence. It is unclear how this state leads to feed forward loops resulting in tumorigenesis. Despite its benign nature, the consistent anatomic origin of ACP in the sellar/suprasellar space, often abutting or involving the hypothalamus, the infundibulum, and the optic chiasm, contributes to multiple long-term complications such as endocrinopathies, obesity, vision loss, and obstructive hydrocephalus. Surgically, the current trend is towards conservative approaches with the goal of maximal safe resection without perturbing the hypothalamus. Adjunct radiotherapy is standard in cases of residual or recurrent disease. Close coordination with endocrinology colleagues is vital to appropriately care for these patients as they often suffer from lifelong endocrinopathies that remain a significant source of burden in this population.

Atypical teratoid rhabdoid tumors (ATRT) are rare, often lethal embryonal tumors of the central nervous system (CNS) that primarily affect very young children. Intensive multimodal approaches have resulted in improvements in survival albeit with significant associated toxicity. Recent molecular studies have led to the discovery of SMARCB1 inactivation and resultant BAF47/INI1 loss as the near-universal key genetic event that leads to widespread epigenetic dysregulation. Rarely, SMARCA4 encoding BRG1 is impacted. SMARCB1 and SMARCA4 are core subunits of the SWI/SNF chromatin remodeling complex, which is a fundamental epigenetic regulator of gene transcription. Up to a third of patients diagnosed with ATRT have Rhabdoid Tumor Predisposition Syndrome (RTPS) characterized by germline SMARCB1 (or SMARCA4) alterations. Patients with RTPS are at increased risk of developing synchronous or metachronous rhabdoid tumors outside the CNS. At least three molecular subgroups of ATRT (ATRT-TYR, ATRT-SHH, ATRT-MYC) have been identified through large-scale DNA methylation and transcriptomic studies, with each subgroup having distinct transcriptional, epigenomic and clinicopathologic features. In this book chapter, we will summarize key epidemiological and clinical features of ATRT, review current conventional multimodal regimens, summarize key findings from conducted prospective trials and recently concluded (2020 to present) meta-analyses, as well as discuss emerging targeted treatment approaches that exploit potential therapeutic vulnerabilities of this epigenetically influenced tumor.

Choroid Plexus Tumors (CPT) are rare (2-4% of all pediatric CNS tumors), predominantly early childhood brain neoplasms. Due to their rarity and the lack of prospective clinical trials, evidence-based treatment guidelines remain limited. This review provides a comprehensive summary of the current knowledge.\n\nCPTs span a spectrum from mature Choroid Plexus Papillomas (CPP) to malignant Choroid Plexus Carcinomas (CPC), with Atypical Choroid Plexus Papillomas (aCPP) in between. A significant proportion of CPCs are driven by either somatic or germline TP53 mutations (Li-Fraumeni syndrome); however, other molecular drivers of CPT tumorigenesis remain poorly understood. CPTs exhibit distinct DNA methylation profiles, allowing for classification into clinically relevant subgroups. These tumors also display a chromosomal instability phenotype, characterized by multiple copy number alterations. \n\nAdvances in molecular profiling have revealed that TP53-mutated CPCs have significantly worse outcomes. Both retrospective and limited prospective data have shown 5-year event-free survival rates of 0-25% for TP53-mutant CPCs versus 70-80% for TP53-wild-type cases. The extent of surgical resection remains another established prognostic factor, while data on the roles of radiation therapy (RT) and myeloablative chemotherapy with stem cell rescue are still evolving. Preliminary evidence suggests that TP53-mutant patients may be getting less benefit from RT, but greater benefit from myeloablative chemotherapy approach with avoidance of RT.\n\n The emerging insights into CPC biology and long-term outcomes can direct the design of future clinical trials. A new international prospective study led by the Pediatric Neuro-Oncology Consortium is in development, with the goal to stratify patients by molecular subtype to receive different therapy based on individual molecular profiles and patient age.

Pediatric-type diffuse low grade glioma are a novel subgrouping of pediatric glioma defined in the updated WHO 2021 classification of central nervous system tumors. The newly recognized pediatric-type diffuse low grade glioma family is comprised of four distinct entities, including diffuse astrocytoma MYB or MYBL1-altered, angiocentric glioma, polymorphous low-grade neuroepithelial tumor of the young, and diffuse low grade glioma MAPK-altered. Due to significant overlap in histopathology and molecular alterations between pediatric-type diffuse low grade glioma, accurate diagnosis of these tumor subtypes requires integration of both histology and molecular findings. Herein, we describe the epidemiologic, imaging, and molecular features of these pediatric diffuse glioma. In addition, we review current knowledge regarding management approach and treatment outcomes, including potential therapeutic implications of prevalent molecular alterations within this family of tumors.

The 7-Dehydrocholesterol reductase (DHCR7), a critical enzyme catalyzing the final step of the cholesterol biosynthesis pathway, has gained attention for its potential role in tumorigenesis. This study systematically investigated the association between DHCR7 expression and oncogenic processes across multiple cancer types.

Tumor progression and therapeutic resistance depend not only on tumor cells but also on the tumor vasculature, a central component of the tumor microenvironment (TME). Accordingly, normalization and remodeling of tumor vessels represent a promising therapeutic strategy, highlighting the urgent need for approaches that selectively and efficiently modulate this compartment. Actrt1 (ArpT1) is an actin-related protein implicated in ciliogenesis, but its roles in the TME are unknown. Here, we show that Actrt1 drives tumor progression through non-hematopoietic cells, with endothelium as a principal site of action. Actrt1 knockout (Actrt1-/-) mice displayed significantly reduced growth of B16F1 and MC38 tumors and improved survival. Bone-marrow chimeras localized this phenotype to the host non-hematopoietic compartment; Actrt1-/- marrow in WT hosts did not confer protection, whereas WT marrow in Actrt1-/- hosts did. Immunofluorescence detected Actrt1 in CD31+ tumor vessels in vivo. Developmental retinal vascularization was preserved, but endothelial sprouting from Actrt1-/- aortic rings was reduced, and recovery after hindlimb ischemia was delayed. In Matrigel-tumor plugs, gross vascular ingrowth was decreased. Single-cell RNA-seq of the GFP- CD45- stromal fraction resolved 14 clusters; the endothelial fraction was unchanged in proportion, yet Actrt1 deficiency shifted its transcriptome toward immaturity. Histology showed shorter, discontinuous CD31+ vessels. Together, our data indicate that Actrt1 promotes tumor growth through non-hematopoietic endothelium by sustaining sprouting and vessel maturation, while developmental angiogenesis remains intact. Targeting Actrt1 may therefore restrain tumor growth by impairing maladaptive angiogenesis and could complement strategies for vascular normalization.

DNA damage response (DDR), a highly complicated regulatory network that detects and repairs DNA lesions, serves as an indispensable guardian of genomic integrity. Targeting aberrant DNA repair pathway has emerged as a promising therapeutic approach for cancer, which includes double-strand break repair (DSBR), nucleotide and base excision repair (NER/BER) and mismatch repair (MMR). Elucidating precise molecular mechanisms of DNA damage repair and their synthetic lethal effects will facilitate the development of novel therapeutic targets and strategies for cancer. Deubiquitinases (DUBs) modulate the subcellular localization, protein activity and stability of DDR molecules, thereby playing a critical role in dynamically orchestrating DNA damage repair process. Furthermore, DUBs are highly attractive drug targets in cancer therapies due to their catalytic domains. This review provides a comprehensive overview of the multifaceted roles and mechanisms of DUBs in DNA damage responses and their anticancer potential.

The atlas of immune microenvironment at single-cell level in BRCA1/2-mutated breast cancer is largely unknown and whether an immune signature on the basis of single-cell atlas is associated with response to neoadjuvant chemotherapy remains to be investigated.

Renal cell carcinoma (RCC) that metastasizes to the pancreas (RCC-PM) is a rare but known phenomenon. These patients have been described to have indolent disease and longer overall survival than patients with metastasis to other sites. We investigated the genomic landscape and outcomes for patients with RCC-PM.

Sturge-Weber syndrome and encephalocraniocutaneous lipomatosis (ECCL) are neurocutaneous syndromes with unique presentations.

Epithelial-mesenchymal transition (EMT) plays a key role in cancer metastasis by promoting changes in adhesion and motility. RNA-binding proteins (RBPs) regulate alternative splicing (AS) during EMT, enabling a single gene to produce multiple protein isoforms that affect tumor progression. Disruption of RBP-AS interactions may disrupt the progress of diseases like cancer. Despite the importance of RBP-AS relationships in EMT, few computational methods predict these associations. Existing models struggle in sparse settings with limited known associations. To improve performance, we incorporate both sparsity constraints and heterogeneous biological data to infer RBP-AS associations.

Genetic abnormalities in ion channels that regulate the depolarization of adrenal glomerular cell plasma membranes have been identified as a cause of primary aldosteronism (PA) due to aldosterone-producing adenoma (APA). This study aimed to evaluate somatic variants in the KCNJ5, CACNA1D, CLCN2, ATP1A1, ATP2B3, GNAQ, GNA11, and CTNNB1 genes, assess the genotype-phenotype correlation, and analyze the outcomes in patients with APA from a heterogenic ethnic population.

Coiled-coil domain-containing protein 86 (CCDC86) expression is correlated with the occurrence of lymphoma. However, the expression of CCDC86 in solid tumors such as nasopharyngeal carcinoma (NPC) and the effects of CCDC86 on tumorigenesis remains unclear. Here we studied both problems using tumor tissue samples from NPC patients, NPC cell lines (in vivo), and a model of transplanted tumor in BALB/c nude mice (in vitro). We found that CCDC86 protein was expressed in all studied cell lines, but its expression in CNE1, CNE2, CNE-2Z, 5-8F, and 6-10B cell lines was higher than in nasopharyngeal epithelium cell lines NP69 and NP460. In tumor tissues obtained from patients with NPC, CCDC86 expression was higher than in normal (adjacent) tissues. Knockdown of CCDC86 gene inhibited colony formation and cell proliferation, but increased apoptosis. In BALB/c nude mice transplanted with CCDC86-knockdown CNE-2Z cells, tumors barely grew in comparison with the controls transplanted with CNE-2Z cells transfected with an empty vector lentivirus. In conclusion, CCDC86 is expressed in NPC tissues and NPC cell lines and is closely associated with NPC tumorigenesis. Our study may provide insights into exploring the novel therapeutic targets for NPC.

Prostate cancer (PCa) is a leading cause of cancer-related mortality, with significant racial disparities in outcomes. Long non-coding RNAs (lncRNAs) MALAT1 and TUG1 are implicated in oncogenic pathways. Aberrant RNA splicing, a hallmark of cancer, is often driven by dysregulation of serine-arginine protein kinase 1 (SRPK1), a key spliceosome regulator. The relationship between lncRNAs of splicing factors in cancer pathways remains underexplored, and thus, this study aimed to elucidate the roles of MALAT1 and TUG1 lncRNAs in relation to the SRPK1 inhibitor SPHINX31 in PCa.