RB1 deletion

Our study aims to systematically evaluate how Chr13q deletion impacts the progression of PC and its susceptibility to treatment. We anticipate that our study will establish a solid foundation of knowledge that can be used to identify aggressive primary PC and the related risk of progressing to lethal CRPC. This will help develop more effective treatments for patients with aggressive and lethal PC, particularly those with Chr13q..

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.

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.

This review provides an overview of the current knowledge on the clinicoradiological features, pathogenesis, histopathology, and treatment of ASCPLT. In addition, we will discuss the differential diagnosis of this new entity.

These findings suggest an alternative therapeutic strategy using sequential targeting of HRD in g BRCA- associated breast cancers through PARP inhibitors prior to CDK4/6i therapy to intercept deleterious RB1 -loss trajectories and thus suppress the emergence of CDK4/6 inhibitor resistance. More broadly, our findings demonstrate how germline-somatic driven genomic configurations shape response to systemic therapy and can be exploited therapeutically as part of biomarker-directed clinical strategies.

Follow-up was 4-90 months, 2 cases had biochemical recurrence and 1 case died from prostate cancer. The mean age at diagnosis of this group of patients with hereditary prostate cancer was 67.55 years, the mean preoperative PSA was 15.44 ng/ml, and their histomorphology was characterized by a high percentage of intraductal carcinoma and cribriform pattern of the prostate.

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

Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.

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

P2, N=54, Recruiting, Rahul Aggarwal | Trial completion date: Dec 2025 --> Apr 2027 | Trial primary completion date: Dec 2025 --> Apr 2027

Our data strongly support investigation of the chemotherapy-free palbociclib and venetoclax combination as an innovative treatment strategy for post-ibrutinib MCL patients without RB1 deletion.

WGD was detected in 41% of samples with greater than 10% tumor fraction in cell-free DNA across three cancer types. While this represents a substantial percentage of advanced cancers, more research needs to be done regarding the impact of these events on clinical outcomes and treatment response. Additionally, co-occurrence of these events with other advanced cancer biomarkers such as microsatellite instability or homologous recombination deficiency was not reported.

Limited clinical follow-up showed no recurrence or metastasis after 1-13 months (median 4.5 months) post-surgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offers insights into the molecular mechanisms underlying this event.

Prostate-lncRNAs were correlated with AR mutational status and response to treatment with enzalutamide, while TME-lncRNAs were associated with RB1 deletions and poor prognosis. Finally, lncRNAs identified between prostate adenocarcinomas and neuroendocrine tumors exhibited distinct expression and methylation profiles. Our findings demonstrate the ability of single-cell analysis to refine our understanding of lncRNAs in mCRPC and serve as a resource for future mechanistic studies.

While exceedingly rarely, FH mutations may be found in uLMS. Confirmation of FH deficiency should not preclude the diagnosis of sarcoma in smooth muscle neoplasms that meet histologic criteria for malignancy.

ASCPLTs lack MDM2 amplification, but a large subset show RB1 deletion and variable expression of CD34. Though initially thought to be the malignant form of spindle cell lipoma, ASCPLTs are benign with local recurrences (∼10-15%) and no well-documented dedifferentiation or metastasis.

Conumee 2.0 is available under open-source license at: https://github.com/hovestadtlab/conumee2. Supplementary data are available at Bioinformatics online.

Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Notably, the development of allograft models and precancerous precursor models from SCLC GEMMs provides complementary approaches to GEMMs to study tumor cell-immune microenvironment interactions and test new therapeutic strategies to enhance response to immunotherapy. Ultimately, the new generation of SCLC models can accelerate research and help develop new therapeutic strategies for SCLC.

P1, N=156, Active, not recruiting, AstraZeneca | Phase classification: P1b --> P1 | Trial completion date: Sep 2023 --> Jun 2024

Establishing an AH liquid biopsy for RB is aimed at addressing 1) our inability to biopsy tumor tissue and 2) the lack of molecular biomarkers for intraocular prognosis. Current management decisions for RB are made based solely on clinical features without objective molecular testing. This prognostic study shows great promise for using AH as a companion diagnostic.

Overall, while the pediatric and adult pHGG have similar outcomes, there are differences in their genomic structures, most notably in adult pHGG harboring a higher SCNA load. Overall, pHGG represent a biologically diverse set of clinically aggressive tumors that warrant further intensive study.

The study identified pathogenic or likely pathogenic germline RB1 sequence variants and copy number variants in 16/18 (89%) bilateral and 6/31(19%) unilateral cases, which is comparable to worldwide data (10-15% unilateral, 80-85% bilateral). Targeted NGS combined with GRACE-PCR significantly reduce the cost of RB1 testing in Sri Lanka, and may widen access for genetic diagnosis of RB patients in other low and middle income countries.

RB1 loss was observed only in the mesenchymal component of onychomatricoma. Our findings suggest that the proliferated nail matrix in onychomatricoma represents reactive hyperplasia of various degrees secondary to neoplastic mesenchymal proliferation. This indicates that onychomatricoma should be recognized as an RB1-deleted soft tissue neoplasm rather than a fibroepithelial neoplasm.

Based on our findings, we hypothesize that FSPs are part of a spectrum of genetically related lesions, namely the 13q/RB1 family of tumors (which includes pleomorphic fibromas and spindle cell/pleomorphic lipomas). Due to the clinical, morphologic, and molecular overlap, we suggest that FSPs are pleomorphic fibromas occurring in the specialized stroma of the genital region.

Longitudinal analysis of CTC by sWGS may offer a new approach for monitoring disease progression to direct therapy in patients with advanced MBC at a time when they are coming towards the end of other treatment options.

We identified genomic alterations (TP53 mutations, FOXA1 and AR amplification, RB1 and BRCA2 deletions) from primary prostate tumors that are predictive of wide-spread metastases and poor outcomes.

We identified genomic alterations (TP53 mutations, FOXA1 and AR amplification, RB1 and BRCA2 deletions) from primary prostate tumors that are predictive of wide-spread metastases and poor outcomes.

Genomic analysis in circulating MCL cells using the EC-NDC assay provides comprehensive information on genetic alterations in MCL leading to better disease characterization and risk assessment. Implementing routine genomic profiling in MCL may be useful in the era of precision medicine and individualized patient management

The rare occurrence of nuclear pleomorphism is underrecognized in MLS and increases the complexity to the diagnosis of liposarcoma. DDIT3 evaluation can be liberally considered in liposarcoma assessment even in the presence of nuclear pleomorphism.

At relapse they received daratumumab based salvage in combination with lenalidomide and then pomalidomide...The first profiled bone marrow was collected during leukapheresis for cilta-cel but due to progressive disease the patient received an FCRL5 directed bispecific, and a second sample was collected at progression after a brief sCR to this agent... This case represents the first known bi-allelic loss of CD38 and acquired loss of FCRL5 expression. These events, along with the loss of BCMA highlight the need for more advanced clinical testing to assess the actionability of the diverse therapeutic targets available to treat patients today.

P2, N=2, Active, not recruiting, Rahul Aggarwal | Recruiting --> Active, not recruiting | N=24 --> 2 | Trial completion date: May 2026 --> Feb 2026 | Trial primary completion date: May 2025 --> Feb 2025

The tamoxifen-induced AgcCreERT2p53flfl(tm) and AgcCreERT2p53flflRbfl+(tm) mutants developed OS in an age dependent manner correlating with periods of growth: the penetrance was inversely correlated with the age of the mice at the time of tamoxifen treatment, from 100% at younger than 2-week-old to nearly zero after 2 months of age, In both of the Cre-driven models, the tumors occurred exclusively in endochondral bones, often in metaphases adjacent to growth plates... The chondrocyte-derived murine OS resembles human OS in histology, cytogenetic complexity, expression profiles and drug responses. Compared to Osx-Cre-driven osteosarcoma models the skeletal distribution of the OS is more reflective of patterns seen in human OS. This is concordant with the known relationship of osteosarcoma to growth plates.

This study, the largest real-world investigation involving Eastern CLL to date, provides an essential foundation for future clinical investigations of CLL in China. Despite patients being younger, having advanced stages at diagnosis, the outcomes did not deviate from those reported in Western studies. The biological difference may contribute to the discrepancy.

Significantly higher CNAB in patients with poor prognosis by E-S grade III, BCLC stage C, and recurrence than patients with good prognosis by grade III, stage A, grade III and nonrecurrence was noted. Further analysis on a large case series to correlate genomic profiling with clinicopathologic classifications could provide evidence for diagnostic interpretation, prognostic prediction, and target intervention on involved genes and pathways.

Using a ML approach that incorporates multiple omic features improves the prediction accuracy for metastatic prostate cancer outcomes significantly. Validation of these models will be needed in independent data sets in future.

Conclusions RNASEH2B protein is frequently lost in mCRPC subclones, with RB1 loss being less common, and may be of critical importance as this discordant loss is most likely to sensitise to PARPi. This needs further exploration in clinical trials of PARPi.

The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.

From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

RAS/BRAF mutations occur in 30%-40% of myeloma cases and are associated with higher tumor burden, higher R-ISS stage, complex karyotype, and shorter overall survival and progression-free survival. These findings support testing for RAS/BRAF mutations in myeloma patients and underscore the potential therapeutic benefits of RAS/BRAF inhibitors.