News - STAG2 mutation

1year

Validation of the Revised 2022 European LeukemiaNet Risk Stratification in Adult Patients with Acute Myeloid Leukemia. (PubMed, Blood Adv)

We aimed to validate the prognostic value of the 2022 ELN classification (ELN22) evaluating 1,570 newly diagnosed AML patients (median age, 56 years) treated with cytarabine-based intensive chemotherapy regimens...In conclusion, the ELN22 risk stratification improves prognostic discrimination in a large cohort of intensively treated AML patients. Given the heterogeneous outcome in patients with MR gene alterations, ranging between those of intermediate and adverse risk patients, we suggest reevaluation of risk allocation in these patients.

1 year ago

Journal

TP53 (Tumor protein P53) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • STAG2 (Stromal Antigen 2) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • EZH2 mutation • STAG2 mutation • ZRSR2 mutation

cytarabine

1year

STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1. (PubMed, EMBO Rep)

STAG1 is unable to compensate for STAG2 loss and chromatin-bound cohesin is severely decreased, while levels of the processivity factor NIPBL remain unchanged, likely affecting DNA looping dynamics. These results illuminate how STAG2 loss modifies the chromatin interactome of Ewing sarcoma cells and provide a list of potential biomarkers and therapeutic targets.

1 year ago

Journal

STAG2 (Stromal Antigen 2) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)

STAG2 mutation

1year

Establishment and characterization of a patient-derived metastatic extraskeletal Ewing sarcoma cell line ES-ZSS-1. (PubMed, Hum Cell)

These genetic features might be relevant to metastasis and resistance to chemotherapy. To summarize, the novel patient-derived ES cell line we developed closely mimics the phenotype and genotype of patient tumors, making it a reliable tool for research on metastatic ES.

1 year ago

Preclinical • Journal • Metastases

EWSR1 (EWS RNA Binding Protein 1) • STAG2 (Stromal Antigen 2) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • TWIST1 (Twist Family BHLH Transcription Factor 1)

STAG2 mutation

1year

A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis. (PubMed, bioRxiv)

STAG2 is a frequently mutated cohesin subunit across several cancers and one of the most important functional suppressors of lung adenocarcinoma. Our findings underscore important roles of STAG2 in suppressing lung tumorigenesis and highlight a STAG2-PAXIP1/PAGR1 tumor-suppressive program that may transcend cancer type.

1 year ago

Journal

KRAS (KRAS proto-oncogene GTPase) • STAG2 (Stromal Antigen 2)

STAG2 mutation

1year

Clinicopathological characteristics and genetic features of young and senior Ewing sarcoma patients. (PubMed, Diagn Pathol)

Clinicopathological characteristics and genetic features in young and senior EwS patients differed significantly. Targeting cell cycle dysregulation based on age subgroup may be a potential therapeutic strategy for Ewing sarcoma.

1 year ago

Journal

CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • EWSR1 (EWS RNA Binding Protein 1) • STAG2 (Stromal Antigen 2) • ERG (ETS Transcription Factor ERG) • CHEK1 (Checkpoint kinase 1) • EPHA3 (EPH receptor A3) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • SLIT2 (Slit Guidance Ligand 2)

CCND1 amplification • CDK4 amplification • STAG2 mutation • CCND1 expression • EWSR1-FLI1 fusion • CCND1-H • EPHA3 mutation • CHEK1 expression

1year

Presence of triple positive driver mutations in JAK2, CALR and MPL in primary myelofibrosis: a case report and literature review. (PubMed, Hematology)

The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy...The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

1 year ago

Review • Journal

JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2) • STAG2 (Stromal Antigen 2) • CALR (Calreticulin)

ASXL1 mutation • SF3B1 mutation • SRSF2 mutation • STAG2 mutation • JAK2 mutation

Jakafi (ruxolitinib)

1year

Untangling the loops of STAG2 mutations in myelodysplastic syndrome. (PubMed, Leuk Lymphoma)

In the last decade, STAG2 cohesin biology has been of great interest given its role in transcriptional activation, association with poorer prognosis, and lack of mutation-specific therapies. This review discusses the clinical landscape of cohesin mutant myeloid malignancies, particularly STAG2 mutant MDS, including molecular features of STAG2 mutations, clinical implications of cohesin mutant neoplasms, and the current understanding of the pathophysiological function of STAG2 mutations in MDS.

1 year ago

Review • Journal

STAG2 (Stromal Antigen 2) • RAD21 (RAD21 Cohesin Complex Component)

STAG2 mutation

1year

Blast phase of chronic myeloid leukemia presenting as early T-cell precursor acute lymphoblastic leukemia. (PubMed, Am J Clin Pathol)

Patients with CML-BP may have ETP-ALL. These patients usually have an aggressive clinical course, requiring intensive therapy, and may benefit from stem cell transplantation.

1 year ago

Journal

ABL1 (ABL proto-oncogene 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD8 (cluster of differentiation 8) • RUNX1 (RUNX Family Transcription Factor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • BCOR (BCL6 Corepressor) • CD33 (CD33 Molecule) • STAG2 (Stromal Antigen 2) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule)

TET2 mutation • CD8 expression • STAG2 mutation

over1year

Sequential ctDNA profiling in patients with advanced non-small cell lung cancer: An interim analysis of the COPE randomized study (ESMO 2024)

This study highlights serial ctDNA profiling's benefits for managing advanced NSCLC, providing real-time genetic data. It offers predictive insights as potential imaging substitutes, enables dynamic treatment adjustments, and identifies resistance to therapies.

over 1 year ago

Clinical • Circulating tumor DNA • Metastases

KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • STAG2 (Stromal Antigen 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

STK11 mutation • STAG2 mutation • NBN mutation

FoundationOne® CDx • FoundationOne® Liquid CDx

over1year

STAG2 mutations regulate 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme. (PubMed, J Biol Chem)

Finally, STAG2 mutation activated Polycomb activity leading to increased H3K27me3 marks, identifying Polycomb signaling a potential target for therapeutic intervention in STAG2-mutant GBM tumors. Together, these findings illuminate the landscape of STAG2-regulated genes, A/B compartments, chromatin loops, and pathways in GBM, providing important clues into the largely still unknown mechanism of STAG2 tumor suppression.

over 1 year ago

Journal

STAG2 (Stromal Antigen 2)

STAG2 mutation

over1year

Synthetic Lethality between Cohesin and WNT Signaling Pathways in Diverse Cancer Contexts. (PubMed, Cells)

Finally, LY2090314 caused gene expression dysregulation mainly involving pathways related to transcription regulation, cell proliferation, and chromatin remodeling. For the first time, our work provides the underlying molecular basis for synthetic lethality due to cohesin mutations and suggests that targeting the WNT may be a promising therapeutic approach for tumors carrying mutated cohesin.

over 1 year ago

Journal • Synthetic lethality

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • STAG2 (Stromal Antigen 2) • RAD21 (RAD21 Cohesin Complex Component) • SMC1A (Structural Maintenance Of Chromosomes 1A)

MYC expression • STAG2 mutation

LY2090314

over1year

Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)

P1, N=32, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Aug 2024 --> Feb 2026 | Trial primary completion date: Feb 2024 --> Aug 2025

over 1 year ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • MECOM (MDS1 And EVI1 Complex Locus) • NUP214 (Nucleoporin 214) • GATA2 (GATA Binding Protein 2) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • DEK (DEK Proto-Oncogene) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

TP53 mutation • FLT3 mutation • RUNX1 mutation • ASXL1 mutation • EZH2 mutation • MLL rearrangement • SRSF2 mutation • U2AF1 mutation • BCOR mutation • Chr del(5q) • STAG2 mutation • FLT3 wild-type • Chr t(9;11) • ZRSR2 mutation

cytarabine • Pemazyre (pemigatinib) • daunorubicin • Starasid (cytarabine ocfosfate)