News - RB1 deletion - LARVOL VERI

Cyclin dependent kinase 4/6 inhibitor palbociclib synergizes with BCL2 inhibitor venetoclax in experimental models of mantle cell lymphoma without RB1 deletion. (PubMed, Exp Hematol Oncol)

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.

1 month ago

Journal • IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • MCL1 (Myeloid cell leukemia 1) • BCL2L1 (BCL2-like 1)

CDKN2A deletion • RB1 deletion • MYC expression • CDK4 overexpression • CDKN2A overexpression • RB deletion

Venclexta (venetoclax) • Ibrance (palbociclib) • Imbruvica (ibrutinib)

2ms

Characterization of whole genome duplication in a genomic cohort of over 14000 cell free DNA samples (AACR 2024)

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.

2 months ago

Cell-free DNA

TP53 (Tumor protein P53) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • WRN (WRN RecQ Like Helicase)

TP53 mutation • HRD • CCNE1 amplification • RB1 deletion

GuardantOMNI

2ms

Atypical spindle cell/pleomorphic lipomatous tumor with sarcomatous transformation: clinicopathologic and molecular analysis of four cases. (PubMed, Mod Pathol)

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.

2 months ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)

RB1 deletion • RB1 expression

2ms

Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer. (PubMed, NPJ Genom Med)

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.

2 months ago

Journal • Metastases

RB1 (RB Transcriptional Corepressor 1)

RB1 deletion • AR mutation • RB deletion

Xtandi (enzalutamide capsule)

2ms

Fumarate-Deficient Uterine Leiomyosarcoma: Molecular Confirmation of Four Cases (USCAP 2024)

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.

2 months ago

Clinical

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • FH (Fumarate Hydratase)

TP53 mutation • MET mutation • RB1 deletion • ATRX mutation • RB deletion

FoundationOne® Heme CDx

3ms

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor. (PubMed, Surg Pathol Clin)

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.

3 months ago

Review • Journal

RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CD34 (CD34 molecule)

MDM2 amplification • RB1 deletion • RB deletion

3ms

Conumee 2.0: Enhanced copy-number variation analysis from DNA methylation arrays for humans and mice. (PubMed, Bioinformatics)

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

3 months ago

Preclinical • Journal • Epigenetic controller

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • RB1 deletion

4ms

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. (PubMed, Cell)

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.

4 months ago

Journal

RB1 (RB Transcriptional Corepressor 1) • FAT1 (FAT atypical cadherin 1) • ZFHX3 (Zinc Finger Homeobox 3) • CASP10 (Caspase 10)

RB1 deletion • RB1 mutation • FAT1 mutation • RB deletion • ZFHX3 mutation

4ms

Genetically-engineered mouse models of small cell lung cancer: the next generation. (PubMed, Oncogene)

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.

4 months ago

Preclinical • Review • Journal • IO biomarker

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)

TP53 deletion • RB1 deletion

5ms

BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)

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

5 months ago

Phase classification • Trial completion date

HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • FGFR (Fibroblast Growth Factor Receptor) • CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)

PD-L1 expression • FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification

Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)

5ms

Aqueous Humor Liquid Biopsy as a Companion Diagnostic for Retinoblastoma: implications for diagnosis, prognosis and therapeutic options. Five years of Progress. (PubMed, Am J Ophthalmol)

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.

5 months ago

Journal • Liquid biopsy • Companion diagnostic • Biopsy

RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

RB1 deletion • RB deletion

6ms

Clinicopathologic characterization of diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype: an aggressive and genomically complex group of tumors affecting children and adults (SNO 2023)

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.

6 months ago

Clinical

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MGMT (6-O-methylguanine-DNA methyltransferase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MDM4 (The mouse double minute 4) • CDK6 (Cyclin-dependent kinase 6)

MET amplification • CDKN2A deletion • MYCN amplification • MGMT promoter methylation • RB1 deletion • MDM4 amplification • IDH wild-type • RB deletion • CDK6 amplification

6ms

RB1 screening of retinoblastoma patients in Sri Lanka using targeted next generation sequencing (NGS) and gene ratio analysis copy enumeration PCR (GRACE-PCR). (PubMed, BMC Med Genomics)

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.

6 months ago

Journal • Next-generation sequencing

RB1 (RB Transcriptional Corepressor 1)

RB1 deletion

6ms

RB1 loss in the mesenchymal component of onychomatricoma. (PubMed, J Cutan Pathol)

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.

6 months ago

Journal

RB1 (RB Transcriptional Corepressor 1) • CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase)

RB1 deletion

6ms

Fibroepithelial Stromal Polyp of the Vulvovaginal Region as Part of the RB1 Family of Tumors: Friend or Foe? (PubMed, Int J Gynecol Pathol)

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.

6 months ago

Journal • Stroma

RB1 (RB Transcriptional Corepressor 1)

RB1 deletion • RB1 expression • RB deletion

6ms

Genomic Analysis of Circulating Tumour Cells for Guiding Treatment Decisions in Patients with Metastatic Breast Cancer. (AMP 2023)

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.

6 months ago

Clinical • Genomic analysis • Circulating tumor cells • Tumor cell • Metastases • Omic analysis

HER-2 (Human epidermal growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • JAK2 (Janus kinase 2) • CDK6 (Cyclin-dependent kinase 6)

HER-2 amplification • RB1 deletion

CELLSEARCH®

7ms

Determinants of Widespread Metastases and of Metastatic Tropism in Patients with Prostate Cancer: A Genomic Analysis of Primary and Metastatic Tumors. (PubMed, Int J Radiat Oncol Biol Phys)

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.

7 months ago

Journal • BRCA Biomarker • Metastases

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • FOXA1 (Forkhead Box A1)

TP53 mutation • RB1 deletion • BRCA2 deletion • BRCA1 deletion • AR amplification • FOXA1 mutation • RB deletion

MSK-IMPACT

7ms

Determinants of Widespread Metastases and of Metastatic Tropism in Patients with Prostate Cancer: A Genomic Analysis of Primary and Metastatic Tumors (ASTRO 2023)

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.

7 months ago

Clinical • Genomic analysis • BRCA Biomarker • Metastases • Omic analysis

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • FOXA1 (Forkhead Box A1)

TP53 mutation • RB1 deletion • BRCA2 deletion • BRCA1 deletion • AR amplification • FOXA1 mutation • RB deletion

MSK-IMPACT

7ms

Comprehensive genomic analysis in Mantle Cell Lymphoma identifies risk factors and predicts patients’ outcome: results from the EU-MCL network trials (DGHO 2023)

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

7 months ago

Clinical • IO biomarker • Genomic analysis • Omic analysis

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • TNFAIP3 (TNF Alpha Induced Protein 3) • CD79A (CD79a Molecule) • BCL3 (BCL3 Transcription Coactivator) • NFKBIE (NFKB Inhibitor Epsilon)

TP53 mutation • ATM mutation • NOTCH1 mutation • Chr t(11;14) • CDKN2A deletion • CDKN2A mutation • RB1 deletion • TP53 amplification

8ms

Myxoid liposarcoma with nuclear pleomorphism: a clinicopathological and molecular study. (PubMed, Virchows Arch)

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.

8 months ago

Journal

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • FUS (FUS RNA Binding Protein) • DDIT3 (DNA-damage-inducible transcript 3)

TP53 mutation • RB1 deletion • TP53 expression • RB deletion

8ms

Longitudinal Profiling Identifies Genetic Mechanisms of Resistance to Four Different Drug Classes in a t(4; 14) Positive Patient (IMW 2023)

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.

8 months ago

Clinical • IO biomarker

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TNFRSF17 (TNF Receptor Superfamily Member 17) • BCL2L11 (BCL2 Like 11) • IKZF3 (IKAROS Family Zinc Finger 3) • SDC1 (Syndecan 1)

CDKN2A deletion • RB1 deletion • SDC1 positive • Chr del(13)(q14)

lenalidomide • Darzalex (daratumumab) • pomalidomide • Carvykti (ciltacabtagene autoleucel)

8ms

Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer (clinicaltrials.gov)

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

8 months ago

Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date

RB1 (RB Transcriptional Corepressor 1) • SYP (Synaptophysin)

RB1 deletion • RB1 mutation

Erleada (apalutamide) • cetrelimab (JNJ-63723283)

8ms

GENERATION OF CHONDROCYTE-DERIVED MOUSE OSTEOSARCOMA MODELS - TRACKABLE SYSTEMS TO DELINEATE ONCOGENIC AND METASTATIC ENVENTS PRIOR TO TUMOROGENESIS (CTOS 2023)

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.

8 months ago

Preclinical • Metastases

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)

RB1 deletion

tamoxifen

9ms

An Investigation into the Differences between Western and Chinese population with Chronic Lymphocytic Leukemia (IWCLL 2023)

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.

9 months ago

Clinical

RB1 (RB Transcriptional Corepressor 1) • IGH (Immunoglobulin Heavy Locus)

IGH mutation • RB1 deletion • RB deletion

9ms

Integrated exome sequencing and microarray analyses detected genetic defects and underlying pathways of hepatocellular carcinoma. (PubMed, Cancer Genet)

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.

9 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDH1 (Cadherin 1) • ALDH2 (Aldehyde Dehydrogenase 2 Family Member) • AXIN1 (Axin 1) • IRF2 (Interferon Regulatory Factor 2) • RPL5 (Ribosomal Protein L5)

RB1 deletion

9ms

Multi-Omic Integration of Blood-Based Tumor-Associated Genomic and Lipidomic Profiles Using Machine Learning Models in Metastatic Prostate Cancer. (PubMed, JCO Clin Cancer Inform)

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.

9 months ago

Journal • Machine learning • Metastases

RB1 (RB Transcriptional Corepressor 1) • CHEK2 (Checkpoint kinase 2)

RB1 deletion • CHEK2 mutation • AR mutation • AR amplification • RB deletion

9ms

RNASEH2B loss and PARP inhibition (parpi) in metastatic castration resistant prostate cancer (mCRPC) (ESMO 2023)

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.

9 months ago

PARP Biomarker • Metastases

RB1 (RB Transcriptional Corepressor 1)

RB1 deletion • DDR signature score

9ms

Genomic alterations related to HPV infection status in a cohort of Chinese prostate cancer patients. (PubMed, Eur J Med Res)

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.

9 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • ERCC2 (Excision repair cross-complementation group 2) • KMT2C (Lysine Methyltransferase 2C) • JAK1 (Janus Kinase 1) • SPOP (Speckle Type BTB/POZ Protein) • FOXA1 (Forkhead Box A1) • FCGR2B (Fc Fragment Of IgG Receptor IIb)

RB1 deletion • KMT2C mutation • SPOP mutation

9ms

Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer. (PubMed, J Ovarian Res)

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.

9 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • NOTCH3 (Notch Receptor 3) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) • PIK3R2 (Phosphoinositide-3-Kinase Regulatory Subunit 2 ) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit) • ZKSCAN1 (Zinc Finger With KRAB And SCAN Domains 1)

RB1 deletion • BRCA2 deletion • BRCA1 deletion

9ms

Plasma cell myeloma with RAS/BRAF mutations is frequently associated with a complex karyotype, advanced stage disease, and poorer prognosis. (PubMed, Cancer Med)

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.

9 months ago

Journal • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • RAS (Rat Sarcoma Virus)

BRAF mutation • NRAS mutation • RAS mutation • RB1 deletion • RB deletion

10ms

Endometrial stromal sarcomas with BCOR alterations: clinicopathological and molecular study of a rare subgroup (ECP 2023)

We also detected a subset of cases with MDM2 and CDK4 amplification, along with CDKN2A and/or RB1 deletion. This emphasizes the clinical relevance of detailed molecular characterization of BCOR-associated ESS to identify potential candidates to CDK4/6 inhibitors.

10 months ago

Clinical • Stroma

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • MDM2 (E3 ubiquitin protein ligase) • BCOR (BCL6 Corepressor) • MME (Membrane Metalloendopeptidase) • JAZF1 (JAZF Zinc Finger 1)

CDKN2A deletion • RB1 deletion • CDK4 amplification • CCND1 expression • MDM2 amplification + CDK4 amplification • RB deletion

10ms

Mammary myofibroblastoma: a clinicopathological analysis of fifteen cases (PubMed, Zhonghua Bing Li Xue Za Zhi)

The schwannoma-like subtype is similar to schwannoma, while the invasive subtype is easily misdiagnosed as fibromatosis-like or spindle cell metaplastic carcinoma. Therefore, it is important to recognize the various histological subtypes and clinicopathological features of the tumor for making correct pathological diagnosis and rational clinical treatment.

10 months ago

Journal

RB1 (RB Transcriptional Corepressor 1) • CD34 (CD34 molecule)

RB1 deletion • RB1 negative

10ms

New Insights Into the Pathogenesis of T-Cell Lymphoma and How This May Guide Treatment (SOHO 2023)

TFHLs, which frequently carry mutations of TET2, DNMT3A, RHOA and IDH2, rarely seen in combination in other PTCL, have a higher response rate to hypomethylating agents such as 5-azacytidine and histone deacetylase inhibitors such as romidepsin. Tumors harboring SVs or amplification of CD274 may show greater sensitivity to immune checkpoint inhibitors. Four tumor microenvironment subgroups defined by expression profiling alone, may represent immunotherapy biomarkers.

10 months ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • JAK1 (Janus Kinase 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • JAK3 (Janus Kinase 3) • RHOA (Ras homolog family member A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • TBX21 (T-Box Transcription Factor 21) • TYK2 (Tyrosine Kinase 2) • DUSP22 (Dual Specificity Phosphatase 22) • GATA3 (GATA binding protein 3) • USP22 (Ubiquitin Specific Peptidase 22)

PD-L1 expression • TP53 mutation • ALK positive • DNMT3A mutation • ALK fusion • NOTCH1 mutation • CDKN2A deletion • TET2 mutation • CDKN2A mutation • RB1 deletion • PD-L1 amplification • ALK negative • STAT3 mutation

azacitidine • Istodax (romidepsin)

11ms

Diagnostic value of MDM2 RNA in situ hybridization for low-grade osteosarcoma: Consistency comparison of RNA in situ hybridization, fluorescence in situ hybridization, and immunohistochemistry. (PubMed, Virchows Arch)

Acid decalcification still has an adverse impact on RNA. Some MDM2-nonamplified tumors may show positivity for MDM2 RNA-ISH, which needs to be analyzed comprehensively in combination with clinicopathological features.

11 months ago

Journal

TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • RB1 deletion • RB1 mutation • MDM2 overexpression • RB deletion

11ms

IDH-mutant astrocytomas with primitive neuronal component are aggressive tumors characterized by alterations in RB1 and TP53 (AANP 2023)

Among IDH1/RB1 co-mutant astrocytomas, the presence of a primitive neuronal component was associated with significantly shorter overall survival (P = 0.022, hazard ratio [HR]: 9.00, 95% CI: 4.17–19.4). Conclusions IDH1/RB1 co-mutant astrocytomas frequently demonstrate a primitive neuronal component, which is associated with characteristic mutations and a highly aggressive disease course.

11 months ago

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2)

TP53 mutation • PTEN mutation • RB1 deletion • ATRX mutation • CDK4 amplification • IDH wild-type

MSK-IMPACT

11ms

Simultaneous Copy Number Alteration and Single-Nucleotide Variation Analysis in Matched Aqueous Humor and Tumor Samples in Children with Retinoblastoma. (PubMed, Int J Mol Sci)

Ultimately, 11/11 cases have somatic alterations identified, including nine RB1 SNVs and 10 recurrent RB-SCNAs with four focal RB1 deletions and one MYCN gain. The results presented show the feasibility of utilizing one sequencing approach to obtain SCNA and targeted SNV data to capture a broad genomic scope of RB disease, which may ultimately expedite clinical intervention and be less expensive than other methods.

11 months ago

Journal

RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

RB1 deletion • RB deletion

12ms

Impact of concurrent tumour events on the prostate cancer outcomes of germline BRCA2 mutation carriers. (PubMed, Eur J Cancer)

gBRCA2-related prostate tumours are enriched for aggressive genomic features, such as BRCA2-RB1 co-deletion and MYC amplification. The presence or absence of these events modify the outcomes of gBRCA2 carriers.

12 months ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)

BRCA2 mutation • MYC amplification • RB1 deletion • BRCA2 deletion • BRCA1 deletion • RB deletion

12ms

Spindle Cell Lipoma and Pleomorphic Lipoma: An Update and Review. (PubMed, Cancer Diagn Progn)

Knowledge of these peculiar tumors is important because it can mimic a variety of benign and malignant soft-tissue tumors. This review provides an updated overview of the clinical, radiological, histopathological, cytogenetic, and molecular genetic features of SCL/PL.

12 months ago

Review • Journal

RB1 (RB Transcriptional Corepressor 1) • CD34 (CD34 molecule)

RB1 deletion

almost1year

Evolution of genomic profiles in primary and recurrent brain gliomas. (ASCO 2023)

The evolutional patterns in glioma depend on clonal selection caused by CNAs, mutations, genetic drift, intratumor heterogeneity and/or the patient’s treatment. Recurrence may arise from one major tumor clone or from one or more subclones within the primary tumor through. Integrated cytogenomic analyses of genetic/epigenetic profiles of primary and all recurrent tissues can contribute to a better understanding of mechanisms responsible for these processes and to identification of new alterations related to gliomas progression and/or resistance to treatment.

almost 1 year ago

TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • RB1 deletion • IDH1 R132H • IDH1 R132 • RB deletion

Archer® VariantPlex® Solid Tumor Kit