Pediatric diffuse low-grade gliomas (LGGs) are heterogeneous group of central nervous system tumors that typically exhibit a relatively benign clinical course. These tumors represent a unique classification in pediatric neuro-oncology, distinct from adult counterparts in terms of biological behavior, molecular pathways, and clinical presentation. The evolving World Health Organization classification system has increasingly relied on combination of histopathologic, genetic, and radiologic criteria to define and distinguish among pediatric glioma subtypes. This article aims to synthesize current knowledge regarding the clinical, molecular, and radiologic features of these pediatric diffuse LGGs and highlights the nuances in diagnosis, treatment approaches, and prognostic outlook.

The 5th edition of the WHO CNS tumor classification (2021) emphasizes molecular alterations, especially in pediatric tumors, integrating histology with molecular profiling for precise diagnosis. Advances like DNA methylation profiling and Next Generation Sequencing have refined tumor subtypes, influencing targeted therapies. Radiogenomics correlates imaging features with genetic profiles, enabling non-invasive tumor characterization, crucial in pediatric cases where biopsies are risky. Artificial intelligence, including machine learning and deep learning, enhances image analysis, segmentation, and prediction of molecular markers, supporting personalized treatment. Despite challenges like data variability and ethical concerns, these technologies promise to revolutionize pediatric neuro-oncology.

Tumor predisposition syndromes (TPS) are inherited cancer syndromes linked to approximately 10% of all cancers and up to 20% pediatric central nervous system (CNS) tumors. TPS manifest with characteristic patterns of neoplasms throughout the body and require targeted, region-specific imaging for surveillance. Advances in cancer genomics have allowed options for therapies targeting specific molecular pathways. This article highlights CNS imaging features of TPS, with additional insights into the underlying genomic alterations that lead to their development.

The in vitro mouse lymphoma assay cell (MLA) is one of the most widely practiced assays in genetic toxicology. MLA detects forward mutations at the thymidine kinase (Tk) locus of the L5178Y (Tk+/- 3.7.2C) cell line derived from a mouse thymic lymphoma. This assay is capable of detecting a wide range of genetic events including point mutations, deletions (intragenic) and multilocus, chromosomal rearrangements, mitotic recombination and non-disjunction. There are two equally accepted versions of the assay, one using soft agar cloning and the second method using liquid media cloning in 96-microwell plates. There are two morphologically distinct types of mutant colonies recovered in the MLA: small and large colony mutants. The induction of small colony mutants is associated with chemicals inducing gross chromosomal aberrations whereas the induction of large mutant colonies is generally associated with chemicals inducing point mutations. The source and karyotype of the cell line as well as the culture conditions are important variables that could influence the assay performance. The assay when performed according to the standards recommended by the International Workshops on Genotoxicity Testing (IWGT) and the Organization of Economic Cooperation and Development Test Guideline 490 is capable of providing valuable genotoxicity hazard information as part of the overall safety assessment process of various classes of test substances.

Breast cancer (BC) is the second leading cause of cancer-related deaths among women, primarily due to late-stage detection and therapy resistance. Therefore, identifying novel therapeutic targets is critical for improving BC outcomes. Long non-coding RNAs (lncRNAs) have recently emerged as promising candidates for cancer prognosis and treatment, owing to their ability to modulate oncogenic signaling pathways. Among them, the tumor-suppressive lncRNA Nkx2-2as has shown inhibitory effects in certain cancers; however, its role in BC remains poorly understood. To the best of our current knowledge, the relationship between Nkx2-2as and the Wnt/β-catenin signaling pathway in BC has not been previously characterized. To address this, we used computational tools including lncHUB2, RPISeq, GeneMANIA, TCGA and ENCORI to predict functional interactions of Nkx2-2as, which guided our focus toward its involvement in the Wnt/β-catenin signaling pathway, a key driver in BC progression. We hypothesized that Nkx2-2as may act as a pharmacologically actionable molecule in this context. To test this, MCF-7 breast cancer cells were transfected with either Nkx2-2as siRNA or an Nkx2-2as-pcDNA3.1 overexpression vector, individually and in combination. Overexpression of Nkx2-2as led to a significant reduction in proliferation (~ 85%), suppression of migration, and increased apoptosis. Conversely, silencing Nkx2-2as enhanced tumorigenic properties. Mechanistic analyses revealed that Nkx2-2as downregulates oncogenic targets such as β-catenin, TCF7 and MYC, while upregulating tumor suppressors AXIN2 and BTG2, the latter being a known inhibitor of β-catenin. Western blot analysis confirmed the transcriptional trends, showing decreased β-catenin and MYC and elevated BTG2 protein levels upon Nkx2-2as overexpression. These findings indicate that Nkx2-2as acts as a negative regulator of Wnt/β-catenin signaling through BTG2 activation, suggesting its potential role as a tumor suppressor and a candidate for RNA-based therapeutic strategies in BC. Targeting the Nkx2-2as/BTG2 axis may provide a conceptual framework for future studies aimed at developing RNA-based interventions to enhance chemosensitivity and overcome therapy resistance in BC.

Infantile hemangiomas (IHs) are the most prevalent noncancerous childhood tumors, affecting up to 10% of infants. IHs develop de novo and following excessive proliferation in the first 4-9 months; they typically degenerate spontaneously in 4-7 years. While treatment is not usually required, 10-15% of cases necessitate clinical or surgical intervention due to functional impairments. Here, we present a complicated capillary IH case, from a clinical and genetic perspective.

Gorlin syndrome (GS) or basal cell nevus syndrome type 1 (BCNS1) is a rare genetic disease belonging to the spectrum of genodermatoses. Here, we present a case with BCNS1 that was caused by haploinsufficiency of PTCH1 gene, which is associated with BCNS1.

Neuroblastoma (NB) is a common pediatric malignant tumor, accounting for approximately 13% of childhood cancer-related deaths. It has a poor prognosis, and its pathogenesis and genetic characteristics remain complex. Although recent studies have suggested a potential association between immune cells and NB, the causal relationship remains unclear. In this study, we utilized genome-wide association studies (GWAS) summary statistics of 731 immune traits (n = 3757) and three NB subtypes: MYCN-amplified NB (n = 5369), 11q-deletion NB (n = 5222), and 1p-deletion NB (n = 5178). We conducted Mendelian randomization (MR) analyses to assess the causal relationship between immune cells (exposure) and these NB subtypes (outcome). After false discovery rate (FDR) correction, neither 11q-deletion NB nor 1p-deletion NB showed significant associations with immunophenotypes. However, and only one immunophenotype was positively correlated with the risk of MYCN-amplified NB: HLA DR on monocyte (OR: 1.754 [95% CI = 1.288 to 2.390], p = 3.6 × 10-4, q value = 0.194). Reverse MR analysis did not support a causal effect of MYCN-amplified NB on HLA DR expression in monocytes. Sensitivity analyses further confirmed the stability and reliability of these findings. Our MR study provides strong evidence for a causal relationship between HLA DR on monocyte and MYCN-amplified NB, suggesting that elevated HLA DR expression may be a risk factor for this aggressive subtype. These findings could inform clinical decision-making regarding prognosis and treatment strategies for MYCN-amplified NB and may also identify potential therapeutic targets.

Galectins are a family of proteins that are involved in various aspects of cancer, including tumor growth, cell migration, invasion, and metastasis. Galectins are subdivided into three families: prototype (such as Gal-1), chimera type (such as Gal-3), and tandem repeat type (such as Gal-9). Despite the evidence linking galectins to the risk of neuroblastoma (NB), the causal association between galectins and NB remains unclear. The primary objective of this study is to clarify the causal effect of galectins (including Gal-1, Gal-3, and Gal-9) on NB risk through a two-sample Mendelian randomization (MR) study. The MR study was performed using summary statistics from extensive genome-wide association studies. Single-nucleotide polymorphisms (SNPs) related to the exposure variables were used as instrumental variables. The primary outcome was NB risk, and the exposure variables included Gal-1, Gal-3, and Gal-9. We chose inverse-variance weighted (IVW), constrained maximum likelihood and model averaging (cML-MA), MR-robust adjusted profile score (MR-RAPS), simple mode, weighted median, and weighted mode as the statistical methods to assess the causal effect; and the IVW method was the primary statistical method. Odds ratio (OR) and 95% confidence interval (CI) were used as the evaluation indices for causality. According to the IVW with fixed-effect results, genetically predicted Gal-9 was associated with an increased risk of NB (OR = 1.639, 95% CI 1.171-2.293, P = 0.004). Similar risk estimates were obtained using cML-MA, MR-RAPS, simple mode, weighted median, and weighted mode. Additionally, the IVW with fixed-effect revealed there was no statistically significant association between Gal-1 and NB (P = 0.605), or between Gal-3 and NB (P = 0.258). No evidence of reverse causality was observed in the MR Steiger test. The results of the leave-one-out sensitivity test confirmed the stability and reliability of the causal effect estimates. This study identified a possible causal association between Gal-9 levels and the risk of NB through a two-sample MR analysis, which might provide preliminary yet insightful findings into the role of Gal-9 in the development of NB. We hope that our findings would promote the exploration of therapeutic strategies for NB.

Recent developments in genetic testing have demonstrated that cancer predisposition syndrome (CPS) is present in approximately 15% of pediatric central nervous system (CNS) tumors; however, the optimal eligibility and timing of germline genetic testing in these patients have not been determined yet.

Afatinib, an irreversible ErbB family inhibitor, is approved for the treatment of non-small cell lung cancer (NSCLC) with both common and selected uncommon EGFR mutations. Evidence in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) is scarce, especially with pharmacokinetic (PK) data. Here, we report the case of a patient with metastatic NSCLC harboring an EGFR G719C mutation who was successfully treated with afatinib during regular hemodialysis. Afatinib was initiated at 20 mg once daily under fasting conditions and later escalated to 30 mg once daily. PK sampling was conducted on two consecutive HD days at each dose level. At 20 mg, the trough concentration (Ctrough) was 4.02 ng/mL, with peak concentrations (Cmax) of 6.09 and 8.75 ng/mL, both lower than reported values in patients with normal renal function. At 30 mg, Ctrough increased to 26.3 ng/mL, while Cmax values of 48.2 and 55.5 ng/mL were comparable to steady-state exposures in patients with preserved renal function. Notably, no adverse events were observed, and the patient has maintained a partial response for over eight months. This case suggests that afatinib can be administered without major dose modification in HD patients, with PK data indicating minimal impact of dialysis and underscoring the importance of accumulating real-world evidence in this underrepresented population.

This phase 1 study aimed to determine the maximum tolerated dose (MTD) and evaluate the safety and preliminary efficacy of rucaparib (RUB), a poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, combined with liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU) in metastatic gastrointestinal (GI) cancers. RUB targets DNA repair pathways, showing efficacy in tumors with homologous recombination deficiency, such as BRCA mutations. Preclinical data suggest synergy with irinotecan, but overlapping toxicities pose challenges.

Afatinib, an irreversible pan-ERBB family inhibitor, has demonstrated promising efficacy in non-small cell lung cancer (NSCLC) patients with uncommon EGFR activating mutations. However, besides the acquisition of the secondary T790M mutation, other resistance mechanisms to afatinib remain to be explored.

Evidence suggests that alternative RNA splicing (AS) plays a critical role in tumor biology and may contribute to the generation of tumor antigens. Here, we develop a method to detect AS in short-read single-cell 5'-RNA-sequencing data, allowing us to uniquely characterize the heterogeneity and dynamic changes in AS in individual cell types within the tumor microenvironment. We identify numerous splicing events specific to either cancer cells or stromal cell types or for triple-negative versus estrogen receptor-positive breast cancers (BCs). By correlating these splice events with expression of splicing regulators in individual cells, we also identify their potential mediators. For instance, we identify and functionally validate the Epithelial Splicing Regulatory Protein-1 (ESRP1) to drive AS in BCs responding to immune checkpoint blockade (ICB). Prioritization of splicing events based on their likelihood to represent tumor antigens reveals that their aggregated load also correlates with high immune activity in multiple cancers, while also predicting expansion of T cells in BCs receiving ICB and prolonging long-term survival of cancer patients treated with ICB. Collectively, our method provides a framework for analyzing AS in single-cell data and defines a key role for AS in the response to ICB.

The metastasis of laryngeal squamous cell carcinoma (LSCC) is not only caused by the tumor itself but is also closely related to cancer-associated fibroblasts (CAFs). The epithelial-mesenchymal transition (EMT) serves as a key event during its metastasis. However, the specific mechanisms underlying LSCC metastasis remain uncertain.

Multifocal micronodular pneumocyte hyperplasia as first manifestation of tuberous sclerosis complex has rarely been reported.

Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia rarely transforms into diffuse large B-cell lymphoma, and there have been no reports of cases proving clonal identity when presenting as primary central nervous system lymphoma. There are many unclear aspects regarding the mechanism by which lymphoplasmacytic lymphoma/Waldenström macroglobulinemia infiltrates the central nervous system and transforms, as well as the treatment methods for the transformed lymphoma.

"Lineage switch" is a term used to describe the phenomenon of change of lineage of acute leukemia to a different lineage. It is typically seen during therapy or at the time of relapse. More commonly, it is described in the pediatric population with an incidence of 6-9%. Lineage switches, though uncommon, can occur from acute myeloid leukemia (AML) to acute lymphoblastic leukemia (ALL (B/T)) and vice versa. The present scenario of AML to B-ALL switch is rare in an adult, with only a handful of cases described in literature. We report herein a case diagnosed as AML at 56 years of age, with NPM mutation who relapsed after 18 months post initial diagnosis. The clinicopathological features, flowcytometry, and molecular characteristics are discussed.

Succinate dehydrogenase (SDH) deficient gastrointestinal stromal tumor (GIST) is the most common type of wild type GIST characterized by lack of mutations in proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDFGR alpha) pathways. It has a unique predilection for females and young adults, with a relatively indolent prognosis and varied treatment modalities. Data regarding SDH GIST from the Indian subcontinent is sparse.

Mammographic density (MD) is a strong, heritable risk factor for breast cancer. To date, 55 independent MD-associated genetic loci have been identified through genome-wide association studies (GWASs) in women of European ancestry; however, no studies have been reported in Asian women.