Morphological diagnosis alone can accurately diagnose lipomas. However, it has a propensity to overdiagnose ALT/WDLPS. Thus, MDM2 FISH should be used more proactively, not only for lesions with obvious morphological abnormalities, but also for lipomatous tumors that are clinically suggestive of ALT/WDLPS.

30 days ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)

MDM2 amplification • CDK4 amplification

Low-Level MDM2 Amplification by FISH: An Institutional Experience With a Diagnostic Dilemma. (PubMed, Int J Surg Pathol)

Laboratory measures and utilizing NGS assay when needed, could be implemented when encountering such problematic "low-level" MDM2 amplification specimens to avoid misdiagnosis and misuse of targeted therapy. Future studies are needed to better characterize and investigate such findings.

1 month ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

MDM2 amplification

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 month ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

Therapy-relevant MDM2 amplification in cholangiocarcinomas in Caucasian patients. (PubMed, Ther Adv Med Oncol)

Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA.

1 month ago

Journal

FGFR2 (Fibroblast growth factor receptor 2) • MDM2 (E3 ubiquitin protein ligase)

TP53 wild-type • MDM2 amplification

brigimadlin (BI 907828)

Primary Liposarcoma of the Spleen: Case Report With Review of the Literature. (PubMed, Int J Surg Pathol)

To the best of our knowledge, this is the first description of a primary liposarcoma of the spleen reported in the literature. Due to the local recurrence risk of liposarcomas, even after R0 resection, we recommended long-term periodic follow-up.

1 month ago

Review • Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

2ms

Primary intracranial dedifferentiated liposarcoma: An extremely rare site with unusual histopathological findings. (PubMed, Neuropathology)

Final diagnosis of DDLS was rendered. The patient had no systemic lesions elsewhere on positron emission tomography computed tomography scan.

2 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)

MDM2 amplification

2ms

Driver mutations associated with signatures of platinum sensitivity in germ cell tumors. (PubMed, NPJ Precis Oncol)

We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance...PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.

2 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • KRAS mutation • KIT mutation • MDM2 amplification • MDM2 mutation

cisplatin

2ms

Malignant epithelioid neoplasm with GLI1 gene rearrangement (PANX3::GLI1 transcript) and MDM2 gene amplification. (PubMed, Virchows Arch)

We discuss the challenges in differential diagnosis from osteogenic tumors and soft tissue neoplasms with epithelioid morphology. Our case is the first report of a tumor with such genetic abnormalities and it is about to replenish the spectrum of rare GLI1-rearranged tumors.

2 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • GLI1 (GLI Family Zinc Finger 1)

MDM2 amplification

2ms

This Study Aims to Find the Best Dose of BI 907828 (Brigimadlin) in Patients With Different Types of Advanced Cancer (Solid Tumors) (clinicaltrials.gov)

P1, N=267, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

2 months ago

Enrollment closed • Metastases

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 wild-type • MDM2 amplification • TP53 amplification

brigimadlin (BI 907828)

2ms

Long-term breast cancer response to CDK4/6 inhibition defined by TP53-mediated geroconversion. (PubMed, Cancer Cell)

Inhibitors of CDK2 can overcome p53 loss, leading to geroconversion and manifestation of senescence phenotypes. Complete inhibition of both CDK4/6 and CDK2 kinases appears to be necessary to facilitate long-term response across genomically diverse HR+ breast cancers.

2 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • RBL2 (RB Transcriptional Corepressor Like 2)

HR positive • MDM2 amplification

3ms

Multi-center external validation of an automated method segmenting and differentiating atypical lipomatous tumors from lipomas using radiomics and deep-learning on MRI. (PubMed, EClinicalMedicine)

The radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics. Hanarth fonds.

3 months ago

Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

3ms

Molecular Analysis of High-Grade Serous Ovarian Carcinoma Exhibiting Low-Grade Serous Carcinoma and Serous Borderline Tumor. (PubMed, Curr Issues Mol Biol)

After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification.

3 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • TP53 wild-type • KRAS G12V • MDM2 amplification • KRAS G12 • TP53 amplification

Avastin (bevacizumab) • paclitaxel

3ms

CDK4 is co-amplified with either TP53 promoter gene fusions or MDM2 through distinct mechanisms in osteosarcoma. (PubMed, NPJ Genom Med)

Additionally, we observed recurring promoter swapping events involving the regulatory regions of the FRS2, PLEKHA5, and TP53 genes. These events resulted in ectopic expression of partner genes, with the ELF1 gene being upregulated by the FRS2 and TP53 promoter regions in two distinct cases.

3 months ago

Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • FRS2 (Fibroblast Growth Factor Receptor Substrate 2) • ELF1 (E74 Like ETS Transcription Factor 1)

MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • TP53 amplification

3ms

The Epidemiology of Biliary Tract Cancer and Associated Prevalence of MDM2 Amplification: A Targeted Literature Review. (PubMed, Target Oncol)

Studies of MDM2 in BTC (N = 19) demonstrated variable frequency of MDM2 amplification according to subtype, with consistently high MDM2 amplification rates in GBC (up to 17.5%), and lower rates in CCA (up to 4.4%). The results from this literature review highlight the geographic heterogeneity of BTC and the need for standardised clinicopathologic assessment and reporting to allow cross-study comparisons.

3 months ago

Review • Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

3ms

Brightline-2: A Study to Test Whether Brigimadlin (BI 907828) Helps People With Cancer in the Biliary Tract, Pancreas, Lung or Bladder (clinicaltrials.gov)

P2, N=103, Recruiting, Boehringer Ingelheim | N=155 --> 103

3 months ago

Enrollment change • Metastases

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 wild-type • MDM2 amplification • TP53 amplification

brigimadlin (BI 907828)

3ms

CD34-positive spindle cell tumour with FGFR1::TACC1 fusion: entity of uncertain behaviour (ECP 2024)

In this particular case, the immunohistochemical and molecular results support a diagnosis of a fibroblastic/myofibroblastic tumour of uncertain behaviour. Notably, there have been no reported cases in the literature of a soft tissue tumour harboring FGFR1::TACC1 fusion as a primary occurrence in this anatomical location. The patient remains in good health without any evidence of disease recurrence at the 5-month follow-up post-surgical intervention.

3 months ago

ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MDM2 (E3 ubiquitin protein ligase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase) • COL1A1 (Collagen Type I Alpha 1 Chain) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)

MDM2 amplification • FGFR1 fusion • CD34 positive

Archer® FusionPlex® Sarcoma kit • FusionPlex® Dx

3ms

Cellular origin and clonal evolution of human dedifferentiated liposarcoma. (PubMed, Nat Commun)

We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β-high immunosuppressive tumor micro-environment.

3 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • TGFB1 (Transforming Growth Factor Beta 1)

MDM2 amplification

3ms

Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and MDM2 Amplification. (PubMed, JCO Precis Oncol)

These preclinical in vivo data provide a rationale for further clinical development of this combinatorial targeted therapy approach.

3 months ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • RET (Ret Proto-Oncogene) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • EGFR mutation • RET fusion • MDM2 amplification

Tagrisso (osimertinib) • Retevmo (selpercatinib) • navtemadlin (KRT-232) • milademetan (RAIN-32)

4ms

Chronic lymphocytic leukemia with MDM2 amplification as an alternative pathway to TP53 dysfunction. (PubMed, Leuk Lymphoma)

No abstract available

4 months ago

Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

4ms

Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53 (clinicaltrials.gov)

P1/2, N=106, Active, not recruiting, Taiho Oncology, Inc. | N=250 --> 106

4 months ago

Enrollment change • Metastases

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

TP53 wild-type • MDM2 amplification

ASTX295

5ms

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (ESMO 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor pts was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

5 months ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • TMB-H • MET amplification • ALK rearrangement • FGFR1 amplification • MDM2 amplification • PTCH1 mutation • BRCA mutation • FGFR3 amplification • PTCH1 rearrangement • NTRK fusion

FoundationOne® CDx

Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

7ms

MDM2 amplification in rod-shaped chromosomes provides clues to early stages of circularized gene amplification in liposarcoma. (PubMed, Commun Biol)

Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.

7 months ago

Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

7ms

HER3 (ERBB3) amplification in liposarcoma - a putative new therapeutic target? (PubMed, World J Surg Oncol)

Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.

7 months ago

Journal • IO biomarker

EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • MDM2 (E3 ubiquitin protein ligase) • DDIT3 (DNA-damage-inducible transcript 3)

MDM2 amplification • ERBB3 amplification

7ms

Primary Cardiac Intimal Sarcoma: Multi-Layered Strategy and Core Role of MDM2 Amplification/Co-Amplification and MDM2 Immunostaining. (PubMed, Diagnostics (Basel))

To summarize, MDM2 amplification and co-amplification, for example, with MDM4, CDK4, HMGA3, CCND3, PDGFRA, TERT, KIT, CCND3, and HDAC9, might improve the diagnosis of PCIS in addition to MDM2 immunostaining since 10-20% of these tumours are MDM2-negative. Further studies are necessary to highlight MDM2 applicability as a prognostic factor and as an element to be taken into account amid multi-layered management in an otherwise very aggressive malignancy.

7 months ago

Review • Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • MDM4 (The mouse double minute 4) • CCND3 (Cyclin D3) • HDAC9 (Histone Deacetylase 9)

MDM2 amplification

8ms

Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2. (PubMed, Histopathology)

Our findings suggest a strong correlation between HMGA2 alteration/MDM2 amplification and a peculiar nuclear atypia, advocating for their evaluation in biphasic tumours to facilitate accurate diagnosis and tailored posttumour removal monitoring. Further studies are warranted to validate these observations and elucidate their prognostic implications.

8 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • HMGA2 (High mobility group AT-hook 2) • WIF1 (WNT Inhibitory Factor 1)

MDM2 amplification • CDK4 amplification • MDM2 overexpression • HMGA2 expression • HMGA2 overexpression

8ms

Diagnosing liposarcoma on (peri)-renal mass biopsy: A clinicopathological study of 30 cases. (PubMed, Histopathology)

When a retroperitoneal tumour is not clinically suspected, histological consideration of a liposarcoma diagnosis may be overlooked. Implementation of ancillary immunohistochemical and cytogenetic testing can ultimately lead to a definitive diagnosis in this potentially misleading anatomical location.

8 months ago

Journal • Biopsy

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

8ms

Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma (clinicaltrials.gov)

P3, N=240, Recruiting, Boehringer Ingelheim | Initiation date: Mar 2023 --> Dec 2023

8 months ago

Trial initiation date • Metastases

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

brigimadlin (BI 907828)

8ms

Imaging features of perinephric myxoid pseudotumors of fat. (PubMed, Abdom Radiol (NY))

PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention.

8 months ago

Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

9ms

Brightline-4: A Study to Test How Well Brigimadlin is Tolerated by People With a Type of Cancer Called Dedifferentiated Liposarcoma (clinicaltrials.gov)

P3, N=240, Recruiting, Boehringer Ingelheim | Initiation date: Dec 2023 --> Mar 2023

9 months ago

Trial initiation date • Metastases

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

brigimadlin (BI 907828)

9ms

Back to the future! Selected bone and soft tissue neoplasms with shared genetic alterations but differing morphological and immunohistochemical phenotypes. (PubMed, Hum Pathol)

Future classification systems in BST neoplasms cannot be solely based on molecular events and ideally will balance morphologic features with molecular analysis. Herein, we provide a narrative literature review of the more common BST neoplasms with shared genetic events but differing demographics, morphology, immunophenotype, and clinical behavior, re-emphasizing the importance of the hematoxylin and eosin slide and the "eye" of the practicing pathologist.

9 months ago

Review • Journal

MDM2 (E3 ubiquitin protein ligase) • EWSR1 (EWS RNA Binding Protein 1) • ATF1 (Activating Transcription Factor 1) • CREB1 (CAMP Responsive Element Binding Protein 1)

MDM2 amplification

10ms

Detection of MDM2 gene amplification by fluorescence in situ hybridization and its diagnostic value in low-grade osteosarcoma (PubMed, Zhonghua Bing Li Xue Za Zhi)

The interpretation criteria for FISH detection of MDM2 amplification are currently not unified. The signal characteristics need more attention when interpreting.

10 months ago

Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

10ms

Superficial dedifferentiated liposarcoma: A clinicopathologic study. (PubMed, Hum Pathol)

These findings emphasize the importance of distinguishing between primary sDDLPS and secondary lesions due to their distinct prognoses. Metastasis or superficial extensions from deep DDLP correlate with a considerably worse prognosis than those originating in superficial tissues.

10 months ago

Journal

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification

10ms

Association of MDM2 Overexpression in Ameloblastomas with MDM2 Amplification and BRAFV600E Expression. (PubMed, Int J Mol Sci)

Overexpression of MDM2 in ameloblastomas is not associated with MDM2 amplification, but most probably with MAPK activation and WTp53 expression. Further verification of those findings could form the basis for the use of MDM2 expression as a marker of MAPK activation in ameloblastomas and the trial of dual BRAF/MDM2 inhibition in the management of MDM2-overexpressing/BRAFV600E-positive/WTp53 ameloblastomas.

10 months ago

Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase)

BRAF V600E • BRAF V600 • TP53 wild-type • MDM2 amplification • TP53 expression • MDM2 overexpression

10ms

DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases. (PubMed, Hum Pathol)

The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

10 months ago

Review • Journal

TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • DDIT3 (DNA-damage-inducible transcript 3)

MDM2 amplification • TP53 expression

10ms

Primary liposarcoma of the uterus with MDM2 negative. (PubMed, Indian J Pathol Microbiol)

Immunohistochemistry showed that the tumor cells were positive for CDK4 but negative for MDM2, and FISH analysis showed no MDM2 amplification. The patient only underwent tumor excision and is currently doing well.

10 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)

MDM2 amplification

10ms

Gene Fusions in Aggressive Testicular Leydig Cell Tumors Likely Represent Events Secondary to Genomic Instability without a Driver Role (USCAP 2024)

TERT fusions were not identified in this series of LCTs, with 2 aggressive metastasizing LCTs harboring non-recurrent NAV3::ASB8 and RAB3IP::TAFA2. These structural variants have not been reported previously and likely represent events secondary to genomic instability without a clear pathogenic role (PMID: 34103665). Whole transcriptome analysis is under way to elucidate additional genomic alterations present in aggressive LCTs.

10 months ago

MDM2 (E3 ubiquitin protein ligase) • NAV3 (Neuron Navigator 3 )

MDM2 amplification

TruSight RNA Pan-Cancer Panel

10ms

CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)

Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.

10 months ago

Tumor mutational burden

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)

TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation

FoundationOne® Heme CDx

10ms

Genomic Insights into Bone Sarcomas Originating from Infarcts (USCAP 2024)

Bone sarcomas associated with infarcts exhibit genomic instability, with pronounced copy number variations, especially in Chromosome 12. CDKN2A/B homozygous deletion is highly prevalent, whereas TP53 alterations appear less frequent than in osteosarcomas. MDM2 amplification and H3.3-G34 mutations are recurrent (33%).

10 months ago

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRD (Homologous Recombination Deficiency) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • MDM2 (E3 ubiquitin protein ligase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

PIK3CA mutation • HRD • MDM2 amplification • CDKN2A deletion • HRAS mutation • HRAS G13R • PIK3CA E542K • PIK3CA E542 • HRAS G13R

TruSight Oncology 500 Assay

10ms

CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)

10 months ago

Tumor mutational burden

TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation

FoundationOne® Heme CDx

11ms

A Case of Myxoid Pleomorphic Liposarcoma with Rhabdoid Cells: A Diagnostic Pitfall. (PubMed, Int J Surg Pathol)

The metastatic lesions contained abundant lipoblasts rather than rhabdoid cells, and we concluded this tumor was a MPLS. The presence of rhabdoid cells could be a diagnostic pitfall, and recognizing such a variation in histology would help improve diagnostic accuracy.

11 months ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • EWSR1 (EWS RNA Binding Protein 1) • FUS (FUS RNA Binding Protein) • DDIT3 (DNA-damage-inducible transcript 3) • MYOD1 (Myogenic Differentiation 1)

MDM2 amplification

11ms

Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy. (PubMed, J Biomed Sci)

Encouragingly, various MDM2 inhibitors have exhibited efficacy in relieving the TIME suppression caused by MDM2. These results demonstrate the prospects for breakthroughs in combination therapy using MDM2 inhibitors and anticancer immunotherapy.

11 months ago

Review • Journal • IO biomarker

MDM2 (E3 ubiquitin protein ligase)

MDM2 amplification