SMAC-2 originated from a metastatic EDP-M-treated ACC in a female patient with hypercortisolism and hyperandrogenism, while SMAC-3 derived from a male patient with a mitotane-treated local recurrence, with no sign of hypercortisolism...Experiments were carried out to study the stability of the two cell lines. SMAC-2 and SMAC-3 display unique molecular and functional features, expanding the repertoire of experimental ACC models and representing valuable tools for preclinical research alongside established cell lines.

2 days ago

Preclinical • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH2 (MutS Homolog 2)

TP53 mutation • CDKN2A deletion

Lysodren (mitotane)

Hemizygous deletion of CDKN2A/B in IDH-mutated glioma: Prognostic impact when adjusting for clinical factors. (PubMed, Neurooncol Adv)

The presence of a hemizygous CDKN2A/B deletion occurs more frequently in astrocytomas compared to oligodendrogliomas at the time of primary diagnosis. Worse survival in patients with astrocytoma and CDKN2A/B hemizygous loss was observed, specifically in WHO grade 2, but this prognostic effect disappeared when adjusting for clinical factors.

2 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion

Clinicopathological and molecular features of meningioma: an analysis of 134 cases based on high-throughput sequencing (PubMed, Zhonghua Bing Li Xue Za Zhi)

TERT promoter mutations and CDKN2A/B homozygous deletion occur exclusively in high-grade meningiomas, link to unfavorable prognosis, and can serve as independent diagnostic markers for WHO grade 3 meningioma. JAK3 mutation seems also to be associated with high-grade meningiomas and shorter survivals.

5 days ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2) • JAK3 (Janus Kinase 3) • KLF4 (Kruppel-like factor 4)

CDKN2A deletion • AKT1 mutation

Spinal high-grade astrocytoma with piloid features arising in a patient with molecularly confirmed cerebellar pilocytic astrocytoma. (PubMed, Neurooncol Adv)

These findings suggest additional molecular alterations associated with tumor progression within the piloid lineage. To our knowledge, this is the first report providing comprehensive, paired molecular characterization of both PA and HGAP in the same patient, offering insight into their potential evolutionary relationship.

7 days ago

Journal

BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KIAA1549

CDKN2A deletion • BRAF fusion

Poor Outcome of Pediatric Patients with Acute Lymphoblastic Leukemia Harboring Low P16 Deletion Ratio: A Post-Hoc Analysis from a Prospective Cohort. (PubMed, Blood Lymphat Cancer)

High-ratio patients exhibited enrichment for RAS mutations (p=0.046). The identified P16 deletion ratio threshold of 0.8 may guide precision risk-adapted therapy in pediatric ALL, but its clinical utility must be validated in larger, diverse cohorts before implementation.

7 days ago

Retrospective data • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

RAS mutation • CDKN2A deletion

Novel genomic risk stratification model for primary high-grade malignant peripheral nerve sheath tumor (MPNST). (PubMed, J Pathol)

Collectively, genomic alterations detected by clinical NGS panels provide potential new biomarkers for risk stratification that can be integrated with conventional parameters to provide improved prognostication and guide therapeutic strategies.

8 days ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

TP53 mutation • TP53 wild-type • CDKN2A deletion

MSK-IMPACT

Genetics and MRD for therapy allocation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia. (PubMed, Blood)

The combination of genetics and MRD allows accurate identification of adult Ph- ALL patients candidates to alloHSCT or chemotherapy. The trial was registered at www.ClinicalTrials.gov: NCT04179929.

9 days ago

Journal

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

TP53 mutation • NRAS mutation • PTEN mutation • CDKN2A deletion • KMT2A rearrangement

13d

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP (clinicaltrials.gov)

P1/2, N=342, Recruiting, Servier Bio-Innovation LLC | Active, not recruiting --> Recruiting | N=104 --> 342

13 days ago

Enrollment open • Enrollment change • First-in-human

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)

CDKN2A deletion • MTAP deletion • IDH wild-type

vopimetostat (TNG462)

13d

Integrated Molecular Profiling Improves Subtype Classification and Reveals Inherited Susceptibility in Medulloblastoma: Insights From a Real-World Cohort. (PubMed, Cancer Med)

Integrated genomic and transcriptomic profiling substantially improves molecular subtyping of MB and reveals inherited risk factors relevant to specific subgroups. Our findings support the implementation of combined molecular diagnostics in routine clinical management of MB and underscore their potential in guiding individualized treatment strategies.

13 days ago

Retrospective data • Journal • Real-world evidence

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCC (FA Complementation Group C)

CDKN2A deletion

17d

S095035 as a Single Agent and in Combination in Adult Participants With Advanced or Metastatic Solid Tumors With Deletion of MTAP (clinicaltrials.gov)

P1/2, N=104, Active, not recruiting, Servier Bio-Innovation LLC | Recruiting --> Active, not recruiting

17 days ago

Enrollment closed • First-in-human

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)

CDKN2A deletion • MTAP deletion • IDH wild-type

vopimetostat (TNG462)

19d

MegaMOST: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (clinicaltrials.gov)

P2, N=455, Recruiting, Centre Leon Berard | Trial completion date: Nov 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Oct 2026

19 days ago

Trial completion date • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF mutation • NRAS mutation • BRAF V600 • KIT mutation • CDKN2A deletion • HRAS mutation • KRAS G12 • PDGFRA mutation • KRAS amplification • NRAS G12

Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)

21d

Beyond cell cycle control: CDKN2A loss is associated with altered NAD+ metabolic states and increased sensitivity to NAMPT inhibition in glioblastoma. (PubMed, Neurooncol Adv)

While CDKN2A loss is classically associated with cell cycle deregulation through the p16-Cdk4-Rb axis, our findings suggest an additional layer of metabolic vulnerability arising from altered NAD+ homeostasis in CDKN2A-deleted glioblastoma, revealing a metabolic-genetic interface for rationally revisiting NAD+ targeting strategies, moving beyond the broad inhibition approaches.

21 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • NAMPT (Nicotinamide Phosphoribosyltransferase)

CDKN2A deletion