RB1 mutation

The median interval between initial retinoblastoma diagnosis and death in the 6 patients who died of their SPMN was 18.8 years (extremes 6.2 and 34.6 years) and between diagnosis of the SPMN and death was 1.2 years (extremes 0.25 and 4 years). Of the patients who had been treated with External Beam Radiotherapy (EBRT), 13 developed a SPMN within the previously irradiated field.

A next-generation sequencing (NGS) panel detected two intronic acceptor splice site variants in the RB1 gene. While the previous literature documents cases of retinocytoma with vitreous seeds, this is the first case to our knowledge of a sporadic multifocal retinocytoma with a large ON prelimiting membrane, subhyaloid seeds, and vitreous seeds associated with two intronic acceptor splice site variants in the RB1 gene and no other detectable mutations.

P2, N=77, Active, not recruiting, Alliance for Clinical Trials in Oncology | Recruiting --> Active, not recruiting

Large-cell basaloid adenocarcinoma is an unusual variant of lung cancer that is easily confused with large-cell neuroendocrine carcinoma. Awareness of this unusual variant of lung adenocarcinoma is important for treatment and prognosis and for avoiding misdiagnosis.

SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCNampRB1+/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCNampRB1+/+ and RB1-/- retinoblastoma subtypes.

We hypothesize that the activation of Dnmt3a, Rb1, and Ezh2 observed in ΔS/N cells may be a consequence of a stress response caused by the accumulation and malfunctioning of Rb1-interacting complexes for the epigenetic reprogramming of Pparγ2/Cebpa and prevention of adipogenesis in an inappropriate cellular context. The failure of ΔS/N cells to differentiate and express Pparγ2 and Cebpa in culture following the expression of the DN Rb1 mutant may indicate the creation of epigenetic memory for new reprogrammed epigenetic states of genes.

Ascl1 loss in established NEPC causes transient regression followed by recurrence, but its deletion before transplantation abrogates lineage plasticity, resulting in castration-sensitive adenocarcinomas. This dynamic model highlights the importance of therapy timing and offers a platform to identify additional lineage plasticity drivers.

Our analysis of the largest number of cLMS cases to-date highlights the importance of large cohort sizes and the exploration beyond small targeted gene panels when performing molecular analyses, as it allowed a comprehensive exploration of the mutational landscape of these tumours and identification of novel candidate driver events. It also uniquely afforded the opportunity to compare the molecular phenotype of cLMS with LMS of other tissue types, such as uterine and soft tissue LMS. Given that molecular profiling has resulted in the development of novel targeted treatment approaches for uterine and soft tissue LMS, our study now allows the same opportunities to become available for patients with cLMS.

The number of CNVs detected in each tumor was between 1 and 7, depending on the age at diagnosis. The analysis of genomic alterations in retinoblastoma is useful to understand the severity of tumor progression and to apply appropriate treatments.

G3NETs are genetically different from NECs. Use of immunohistochemistry for p53 in addition to histomorphology may facilitate accurate categorization of NEC and G3NET. Mutated p53 may also be used as an independent prognostic marker in neuroendocrine tumors of GIT and pancreas.

There were delayed but persistent DNA repair mechanisms in RB1+/- osteocytes, which were sufficient to maintain genomic integrity, thereby preventing or delaying the onset of tumors. This contrasts with our earlier observation of increased mineralization without corresponding gene expression changes, emphasizing the importance of high-throughput analysis over preselected gene set analysis in comprehending functional assay results.

Our study yields valuable insights into the genetic characteristics of LS-SCLC patients with and without BM, aiding the development of personalized treatment strategies. Identifying risk factors associated with the incidence and timing of BM, within the standard regimen of dCRT followed by PCI, may help optimize clinical decision-making for LS-SCLC.

The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

This study indicated high concordance between IHC and NGS findings for RB1/RB1 and p53/TP53 in t-NEPC. We provide a comprehensive benchmark of NGS performance compared with IHC, and these findings may help increase the diagnostic sensitivity of t-NEPC.

No recurrence was detected with a 4-year follow-up. The patient was initially diagnosed with unilateral retinoblastoma, but later developed the disease in the contralateral eye during treatment, which was a case of metachronous bilateral retinoblastoma.

Patients received 4-6 cycles of adebrelimab (20 mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100 mg/m2, D1-3, Q3W and cisplatin, 75 mg/m2, D1, Q3W or carboplatin, AUC = 5, D1, Q3W). This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

Our findings highlight the potential for cfDNA assays to detect mosaic RB1 variants with VAFs as low as 1%. Mosaicism for RB1 should be examined for any RB patient undergoing cfDNA testing where an RB1 variant persists despite no clinical evidence of disease. Enhanced detection of mosaicism in RB1 can allow for optimal counseling, treatment, and surveillance.

In addition, we also observed that the component of immunological cells was regulated by RB1 mutations through the stronger cell-to-cell interactions between epithelial scissor+ cells and immune cells in smokers. This study highlighted that RB1 mutations could drive smoking-related bladder tumorigenesis through inhibiting cytochrome P450 pathway and regulating tumor immune microenvironment.

Therefore, molecular screening is critical for genetic counseling regarding the risk for inherited Rb in unilateral cases, including those with no family history, regardless of the age at diagnosis. However, germline mutations did not appear to significantly predict patient outcomes regarding eye salvage, metastasis, and survival.

Conclusions : Genomic and transcriptomic biomarkers of tissue and peripheral blood were discovered. These biomarkers displayed association with clinical benefit of adebrelimab plus chemotherapy and adebrelimab with consolidate TRT, but further verification was warranted.

Ami+laz had significantly lower rates of EGFR and MET resistance alterations with trends for lower rates of TP53 resistance mutations and RB1 loss compared with osi. These initial findings suggest that first-line ami+laz is changing the biology of acquired resistance and demonstrate clear proof of mechanism with potent inhibition of resistance via the EGFR and MET pathways.

This study demonstrated that the established cryopreserved PDC has the aggressive characteristics of osteosarcoma, in particular the chemoresistance phenotype that might be used for further investigation in the chemoresistant mechanism of osteosarcoma. In conclusion, the approach we applied for primary cell culture might be a promising method to generate in vitro models for functional testing of osteosarcoma.

Integrated and regular bioinformatics analyses found important miRNAs in patients' and miR-20a, miR- 191, and miR-135a can distinguish non-invasive and invasive retinoblastoma, suggesting further research.

In conclusion, the molecular landscape of CS is dominated by TP53 mutations, reinforcing the observation that the majority of these tumors develop from high-grade serous carcinoma. Whether CS cells in serous effusions differ from their counterparts in solid lesions remains uncertain.

The study provides novel insights into the metabolic phenotype of heterozygous RB1 mutant suggesting dysregulation of energy metabolism and glycolytic pathways to be first step even before the changes in cellular proliferation or other phenotypic consequences ensue.

P2, N=80, Not yet recruiting, Centre Leon Berard

P=N/A, N=88, Active, not recruiting, Institut Curie | Recruiting --> Active, not recruiting | N=167 --> 88

P2, N=2, Active, not recruiting, Rahul Aggarwal | Trial completion date: Feb 2026 --> Feb 2025 | Trial primary completion date: Feb 2025 --> Mar 2024

Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.

P=N/A, N=13, Active, not recruiting, Fundació Sant Joan de Déu | Recruiting --> Active, not recruiting | Phase classification: P1 --> PN/A | Trial completion date: Jun 2022 --> Jul 2024 | Trial primary completion date: Jun 2022 --> Jun 2024

The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered...The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

The diagnosis and treatment of retinoblastoma necessitate consideration of numerous factors, including disease staging, germline mutation status, family psychosocial factors, and the resources available within the institution. This review has systematically compiled and categorized the latest developments in the diagnosis and treatment of retinoblastoma which enhanced the quality of care for this pediatric malignancy.

RB1 mutations and high fragmentation ratios correlated with early disease recurrence. Analyzing ctDNA could help in predicting early treatment failure and making clinical decisions for high-risk patients.

We also detected multiple chromosomal gains confined to the high-grade regions, consistent with imbalanced chromosome duplication. These findings broaden our understanding of the molecular pathogenesis of ChRCC and suggest that subclonal RB1 mutations can drive the evolution to high-grade, non-sarcomatoid ChRCC.

Accordingly, NFYC-AS1-depleted cells are stuck in mitosis, indicating defects in mitotic progression. Overall, NFYC-AS1 emerged as a cell cycle-regulating asRNA with dual action, holding therapeutic potential in different cancer types, including the very aggressive RB1-mutated tumors.

We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

Compared to traditional clinicopathologic models, genomic risk stratification demonstrates superior prediction of clinical outcome in STLMS and is comparable in ULMS.

The expression of farnesyltransferase β, which is essential for RAS maturation, was found to be downregulated following RB1 depletion also in an RBL2/p130-dependent manner. These findings unveiled an unexpected mechanism whereby normal mammary epithelial cells resist to tumor initiation upon RB1 LOF.

Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material.

Putative targetable genes and biomarkers in GEPNEC were identified in 22.2% of the patients, and they had longer progression-free survival (PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40 (0.21-0.75), P=0.006]. This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

P=N/A, N=2136, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed