News - SETD2 mutation

Automated real-world data integration improves cancer outcome prediction. (PubMed, Nature)

We demonstrate the feasibility of automated annotation from unstructured notes and its utility in predicting patient outcomes. The resulting data are provided as a public resource for real-world oncologic research.

8 days ago

Journal • Real-world evidence • IO biomarker • Real-world

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

24d

Sudden Blast Crisis in a chronic myeloid leukemia patient in Treatment Free Remission: A case report and literature review. (PubMed, Acta Haematol)

This case, along with others, emphasizes the necessity of implementing a long-term monitoring strategy following TKI discontinuation due to the potential for late onset of blast crisis. Systematic genetic studies in patients failing TFR should be properly carried out to further understand the mechanism and eventually, to predict or prevent such adverse event in patients in TFR.

24 days ago

Review • Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

24d

Acute myeloid leukemia with NPM1, IDH2, and SETD2 mutations mimicking acute promyelocytic leukemia: A case report and literature review. (PubMed, Medicine (Baltimore))

The comprehensive evaluation of bone marrow morphology, immunology, cytogenetics, and molecular biology is essential for the accurate diagnosis of acute myeloid leukemia.

24 days ago

Review • Journal

IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

NPM1 mutation • SETD2 mutation

Venclexta (venetoclax) • azacitidine

2ms

Differences in mutations across tumour sizes in clear-cell renal cell carcinoma. (PubMed, BJU Int)

Large and small ccRCCs are genomically different. Aggressive mutations, namely, SETD2, BAP1, and CDKN2A loss, are rarely observed in small ccRCCs and are observed more frequently in larger tumours. However, when present in tumours ≤7 cm, SETD2 mutations and CDKN2A loss were still independently associated with invasive disease, metastasis, worse survival, and recurrence after resection, after controlling for size.

2 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VHL (von Hippel-Lindau tumor suppressor) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

CDKN2A mutation • PBRM1 mutation • BAP1 mutation • VHL mutation • SETD2 mutation

2ms

Glioma oncogenesis in the Constitutional mismatch repair deficiency (CMMRD) syndrome. (PubMed, Neurooncol Adv)

CMMRD-associated gliomas have a specific oncogenesis that does not involve usual pathways and mutations seen in sporadic pediatric or adult glioblastomas. Frequent alterations in other pathways such as MAPK may suggest the use of other targeted therapies along with PD1 inhibitors.

2 months ago

Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • POLD1 (DNA Polymerase Delta 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • DICER1 (Dicer 1 Ribonuclease III) • EPHB2 (EPH Receptor B2) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)

PD-L1 expression • POLD1 mutation • SETD2 mutation • POLE mutation + POLD1 mutation

7ms

MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level. (PubMed, Cancer Biol Ther)

Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-β pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management.

7 months ago

Journal

CD8 (cluster of differentiation 8) • mTOR (Mechanistic target of rapamycin kinase) • BAP1 (BRCA1 Associated Protein 1) • MUC16 (Mucin 16, Cell Surface Associated) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • TGFB1 (Transforming Growth Factor Beta 1) • CSMD3 (CUB And Sushi Multiple Domains 3)

BAP1 mutation • MTOR mutation • TTN mutation • SETD2 mutation

7ms

Proteogenomic Characterization Reveals Estrogen Signaling as a Target for Never-Smoker Lung Adenocarcinoma Patients without EGFR or ALK Alterations. (PubMed, Cancer Res)

Collectively, this study enhanced our understanding of NENA NSLA by elucidating the proteogenomic landscape and proposed saracatinib as a potential treatment for this patient population that lacks effective targeted therapies. The proteogenomic landscape in never-smoker lung cancer without known driver mutations reveals prognostic proteins and enhanced estrogen signaling that can be targeted as a potential therapeutic strategy to improve patient outcomes.

7 months ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • LLGL2 (LLGL Scribble Cell Polarity Complex Component 2) • ST14 (ST14 transmembrane serine protease matriptase)

STK11 mutation • ALK fusion • ROS1 fusion • SETD2 mutation

saracatinib (AZD0530)

8ms

Clinicopathological and molecular genetic alterations in monomorphic-epitheliotropic intestinal T-cell lymphoma of the small intestine. (PubMed, Eur J Med Res)

Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

8 months ago

Journal • IO biomarker

TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • BCOR (BCL6 Corepressor) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • JAK3 (Janus Kinase 3) • NCAM1 (Neural cell adhesion molecule 1) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • ITGAE (Integrin Subunit Alpha E) • SPN (Sialophorin)

TP53 mutation • CD8 expression • BCOR mutation • JAK3 mutation • SETD2 mutation

8ms

From the archives of MD Anderson Cancer Center: Monomorphic epitheliotropic intestinal T-cell lymphoma: A case with an unusual immunophenotype and discussion of differential diagnosis. (PubMed, Ann Diagn Pathol)

Retreatment led to another one-year interval of clinical remission, but at last follow up the patient has relapsed disease involving the ileum and colon. We also discuss the differential diagnosis of MEITL.

8 months ago

Review • Journal • IO biomarker

ALK (Anaplastic lymphoma kinase) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • TNFRSF8 (TNF Receptor Superfamily Member 8) • CCND1 (Cyclin D1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • GZMB (Granzyme B) • IRF4 (Interferon regulatory factor 4) • MME (Membrane Metalloendopeptidase) • CD7 (CD7 Molecule) • CD99 (CD99 Molecule) • B3GAT1 (Beta-1,3-Glucuronyltransferase 1)

SETD2 mutation

9ms

PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer. (PubMed, iScience)

In vitro, PBRM1 knockdown promoted resistance to cisplatin through boosting STAT3 signaling in cervical cancer cells, while it sensitized tumor cells to poly-ADP-ribose-polymerase inhibitor olaparib. These findings suggest that mutant PBRM1 is a potential ctDNA marker of emerging resistance to NACT and of increased sensitivity to olaparib, which warrants further clinical validation.

9 months ago

Journal • PARP Biomarker • Circulating tumor DNA

ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • PBRM1 (Polybromo 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

PBRM1 mutation • ROS1 mutation • SETD2 mutation

Lynparza (olaparib) • cisplatin

10ms

A missense SNP in the tumor suppressor SETD2 reduces H3K36me3 and mitotic spindle integrity in Drosophila. (PubMed, Genetics)

These data indicate the Set2 E741Q SNP affects both histone methylation and spindle integrity. Moreover, this work further suggests the SETD2 E902Q SNP may hold clinical relevance.

10 months ago

Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

10ms

Chromosome 3p gene alterations as biomarkers for immunocombinations in metastatic renal cell carcinoma: A hypothesis-generating analysis. (PubMed, Pathol Res Pract)

Our data shows a possible negative predictive role of SETD2 GA for ICI-based therapy in RCC. Concomitant VHL and PBRM1 GA could act as a predictor for ICI/TKI efficacy. Our hypothesis-generating analysis highlights the need of an integrated evaluation of these genes as promising biomarkers in RCC. Further larger studies are required.

10 months ago

Journal • IO biomarker • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • VHL (von Hippel-Lindau tumor suppressor) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)

PBRM1 mutation • VHL mutation • SETD2 mutation

10ms

Identification of molecular characteristics of FUT8 and alteration of core fucosylation in kidney renal clear cell cancer. (PubMed, Aging (Albany NY))

Two CF-related subtypes with distinct prognosis and TME were identified in KIRC. FUT8 exhibited elevated expression in KIRC samples.

10 months ago

Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • DNAH9 (Dynein Axonemal Heavy Chain 9) • FUT8 (Fucosyltransferase 8)

SETD2 mutation

11ms

Tumor cell-intrinsic SETD2 inactivation sensitizes cancer cells to immune checkpoint blockade through the NR2F1-STAT1 pathway. (PubMed, J Immunother Cancer)

These findings provide novel insights into the biology of SETD2 inactivation regulation and reveal a new potential therapeutic biomarker for ICIs immunotherapy in various refractory cancers.

11 months ago

Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker • Checkpoint block • Tumor cell

CD8 (cluster of differentiation 8) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • NR2F1 (Nuclear Receptor Subfamily 2 Group F Member 1)

SETD2 mutation

12ms

Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway. (PubMed, Clin Transl Med)

Our results demonstrated that SETD2 inhibits the RAS/ERK signaling pathway by facilitating the transcription of DUSP7 in SMAD4-deficient CRC, which could provide a potential therapeutic target for the treatment of advanced CRC.

12 months ago

Journal

SMAD4 (SMAD family member 4) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • USP7 (Ubiquitin Specific Peptidase 7)

SMAD4 mutation • SMAD4 deletion • SETD2 mutation

SCH772984

12ms

Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma. (PubMed, Ann Diagn Pathol)

These findings justify the use of molecular testing to detect these mutations, especially when we encounter high-grade ccRCC. Detecting SETD2 and BAP1 mutation in ccRCC is useful for risk stratification and proper therapeutic strategy.

12 months ago

Journal • BRCA Biomarker • Metastases

BAP1 (BRCA1 Associated Protein 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

BAP1 mutation • SETD2 mutation

1year

A hypothesis generating analysis of the role of chromosome 3p-related genes as predictors for immunocombinations in metastatic renal cell carcinoma (mRCC) (EMUC 2023)

Our hypothesis-generating data highlights the need of an integrated evaluation of 3p-related genes as promising biomarkers in RCC. Further and wider studies are required.

1 year ago

IO biomarker • Metastases

PBRM1 mutation • VHL mutation • SETD2 mutation

1year

Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential selection for adjuvant therapy (EMUC 2023)

Presence of somatic “non-VHL” mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions These findings support the prognostic value of “non-VHL” mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant therapy.

1 year ago

Clinical

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • mTOR (Mechanistic target of rapamycin kinase) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • NF2 (Neurofibromin 2) • VHL (von Hippel-Lindau tumor suppressor) • TSC2 (TSC complex subunit 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • TSC1 (TSC complex subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • KDM5C (Lysine Demethylase 5C)

ATM mutation • PTEN mutation • PBRM1 mutation • BAP1 mutation • VHL mutation • TSC1 mutation • TSC2 mutation • MTOR mutation • SETD2 mutation

1year

EVALUATION OF GENOMIC AND TRANSCRIPTOMIC ALTERATIONS AND INTRATUMORAL HETEROGENEITY IN SMALL RENAL MASSES UPSTAGED TO PATHOLOGIC T3A CLEAR CELL RENAL CELL CARCINOMA (SUO 2023)

This study identifies genomic and transcriptomic differences between cT1b tumors that remain pT1b versus those that convert to pT3a. These results highlight potential alterations for use as prognostic biomarkers to risk stratify patients and guide decisions regarding active surveillance vs treatment. Future research will focus on evaluating whether these alterations can be identified on prospectively collected standard-of-care RMB specimens.

1 year ago

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

1year

Whole Genome and Transcriptome Sequencing of 21 Paired Chronic and Blast Phase CML Cases: Acquisition of Genomic Alterations, Changes in the Transcriptomic Profiles and Occurrence of B-Cell Receptor Rearrangements (ASH 2023)

1) Extensive genetic profiling indicated a substantial clonal evolution in the progression from CP to BP CML including loss of ASXL1 mutations, expansion of RUNX1 mutated clones, multiple CNA, and the frequent acquisition of a BCR rearrangement in BP with a transcriptomic phenotype resembling B-ALL. 2) A subset of CML cases in CP already showed a transcriptomic phenotype resembling acute leukemia indicating a rapid progression to BP. 3) The presence of a RUNX1 mutated subclone or a clonal BCR rearrangement seem to represent a warning signal in CML CP.

1 year ago

Clinical

ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • WT1 (WT1 Transcription Factor) • BCOR (BCL6 Corepressor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MECOM (MDS1 And EVI1 Complex Locus) • MGA (MAX Dimerization Protein MGA) • MLLT3 (MLLT3 Super Elongation Complex Subunit)

DNMT3A mutation • RUNX1 mutation • ASXL1 mutation • CDKN2A deletion • TET2 mutation • MLL rearrangement • BCOR mutation • IKZF1 deletion • WT1 mutation • MECOM rearrangement • SETD2 mutation • ABL1 fusion • MGA mutation • MLL3 mutation

1year

SETD2 mutations do not contribute to clonal fitness in response to chemotherapy in childhood B cell acute lymphoblastic leukemia. (PubMed, Leuk Lymphoma)

SETD2 mutations affected the chromatin landscape and transcriptional output that was unique to each cell line. Collectively our data does not support a role for SETD2 mutations in driving clonal evolution and relapse in B-ALL, which is consistent with the lack of enrichment of SETD2 mutations at relapse in most studies.

1 year ago

Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

1year

Identification of the H3K36me3 reader LEDGF/p75 in the pancancer landscape and functional exploration in clear cell renal cell carcinoma. (PubMed, Comput Struct Biotechnol J)

In summary, the present study identified that LEDGF/p75 may serve as a prognostic predictor for tumors such as adrenocortical carcinoma, kidney chromophobe, liver hepatocellular carcinoma, pancreatic adenocarcinoma, skin cutaneous melanoma, and clear cell renal cell carcinoma (ccRCC). In addition, in vitro experiments and gene microarray sequencing were performed to explore the function of LEDGF/p75 in ccRCC, providing new insights into the pathogenesis of the nonmutated SETD2 ccRCC subtype.

1 year ago

Journal • Pan tumor

KMT2A (Lysine Methyltransferase 2A) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

1year

Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2 (clinicaltrials.gov)

P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

1 year ago

Trial completion date • Trial primary completion date • Metastases

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

adavosertib (AZD1775)

1year

Investigating the Role of FoxP3 in Renal Cell Carcinoma Metastasis with BAP1 or SEDT2 Mutation. (PubMed, Int J Mol Sci)

Using an in vivo nude mice orthotopic kidney cancer model, we found that silencing FoxP3 could inhibit tumor growth. In conclusion, our study demonstrated that BAP1 or SEDT2 mutation could lead to higher expression of FoxP3 in RCC patients, and FoxP3 could eventually stimulate RCC cells' invasion and metastasis, which might indicate that FoxP3 could function as a potential oncogene in RCC progression.

1 year ago

Journal

BAP1 (BRCA1 Associated Protein 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • FOXP3 (Forkhead Box P3)

BAP1 mutation • FOXP3 overexpression • SETD2 mutation • FOXP3 expression

over1year

A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation. (PubMed, BMC Cancer)

This suggests a new role for SETD2 loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict SETD2 mutation status with high accuracy and correlates with patient prognosis.

over 1 year ago

Journal • Epigenetic controller

TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

over1year

SETD2 loss and ATR inhibition synergize to promote cGAS signaling and immunotherapy response in renal cell carcinoma. (PubMed, Clin Cancer Res)

SETD2 loss and ATR inhibition synergize to promote cGAS signaling and enhance immune cell infiltration, providing a mechanistic rationale for the combination of ATR and checkpoint inhibition in RCC patients with SETD2 mutations.

over 1 year ago

Journal • IO biomarker

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CGAS (Cyclic GMP-AMP Synthase)

SETD2 mutation

berzosertib (M6620)

over1year

Targetable gene fusions and other alterations in central nervous system tumors assessed by RNA and DNA-based next-generation sequencing (ESMO 2023)

Conclusions The combination of RNA- and DNA-based NGS provides information about molecular alterations for the management of patients with CNS tumors. Those with actionable gene fusions or other alterations may benefit from target therapy, especially in the setting of limited choice of treatments.

over 1 year ago

Next-generation sequencing

BRAF (B-raf proto-oncogene) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KIAA1549 • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1) • RELA (RELA Proto-Oncogene) • ZFTA (Zinc Finger Translocation Associated)

CDKN2A deletion • CDKN2A mutation • KIAA1549-BRAF fusion • FGFR1 fusion • MET fusion • SETD2 mutation

OncoScreen Plus®

over1year

The characteristics in Chinese NSCLC patients with different BRAF mutation classes (ESMO 2023)

Furthermore, TP53, LRP1B, STK11, SPTA1and MAGI2 were significantly over-mutated in Class II and III (p<0.06) and SETD2 is over-mutated in Class I (p<0.001), might suggesting relatively poor prognosis in NSCLC patients. Conclusions The characteristics of Chinese NSCLC were further explored, including BRAF mutation types, the incidence of related co-mutations and TMB value, which is helpful to formulate targeted therapy strategies to adapt to different types of BRAF mutation functions according to their genomic and clinical characteristics.

over 1 year ago

Clinical • IO biomarker

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • LRP1B (LDL Receptor Related Protein 1B) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • SPTA1 (Spectrin Alpha)

TP53 mutation • BRAF V600E • BRAF mutation • BRAF V600 • STK11 mutation • BRAF K601E • BRAF D594G • BRAF G469A • BRAF L597R • BRAF G466A • SETD2 mutation • BRAF K601 • BRAF L597

over1year

Genomic traits of therapeutic response to anti-PD-1 therapy in peripheral T cell lymphoma (ESMO 2023)

Methods We enrolled 89 peripheral T cell lymphoma (PTCL) patients in phase II clinical trial of geptanolimab and performed targeted next-generation sequencing for 440 cancer-associated genes...Conclusions In this study we comprehensively depicted the pre-treatment mutation profiles of PTCL and identified genetic alterations with prognostic value for anti-PD-1 therapy. Notably, we found JAK3 mutations which are vital and prevalent in PTCL reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense.

over 1 year ago

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

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • KMT2C (Lysine Methyltransferase 2C) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • JAK3 (Janus Kinase 3) • PI3K (Phosphoinositide 3-kinases)

PD-L1 expression • TP53 mutation • TMB-H • JAK3 mutation • JAK3 M511I • SETD2 mutation

Aibining (geptanolimab)

over1year

SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy. (PubMed, BMC Cancer)

We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.

over 1 year ago

Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

TMB-H • MSI-H/dMMR • HRD • SETD2 mutation

over1year

SETD2 loss in renal epithelial cells drives epithelial-to-mesenchymal transition in a TGF-β-independent manner. (PubMed, Mol Oncol)

Public expression data from SETD2 wild-type/mutant ccRCC support the EMT transcriptional signatures derived from cell line models. In summary, our studies reveal that SETD2 is a key regulator of EMT phenotypes through cell-intrinsic and cell-extrinsic mechanisms that help explain the association between SETD2 loss and ccRCC metastasis.

over 1 year ago

Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • SOX2 • TGFB1 (Transforming Growth Factor Beta 1) • PRRX1 (Paired Related Homeobox 1)

SETD2 mutation

over1year

New insights into the clinical characteristics of SETD2-mutated acute myeloid leukaemia. (PubMed, Br J Haematol)

SETD2-mutated patients saw excellent therapeutic responses but failed to gain better survival time than other patients. This could be because of the high recurrence and mortality in SETD2-mutated patients who have additional mutations, such as NRAS mutation.

over 1 year ago

Journal

NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

NRAS mutation • CEBPA mutation • SETD2 mutation

over1year

SETD2-H3K36ME3: an important bridge between the environment and tumors. (PubMed, Front Genet)

As a key component of common tumor suppressor mechanisms, SETD2-H3K36me3is an important target for clinical disease diagnosis and treatment. Here, we reviewed the structure and function of the SETD2 and how SETD2-H3K36me3 functions as a bridge between the environment and tumors to provide an in-depth understanding of its role in the occurrence and development of various tumors, which is of great significance for future disease diagnosis and treatment.

over 1 year ago

Review • Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation

over1year

Intramedullary tumor in adult with 1p/19q codeletion, FGFR1 mutation and DNA methylation profile of diffuse leptomeningeal glioneuronal tumor (AANP 2023)

DNA MP yielded a match with DLGNT though somewhat incongruent radiographic findings were present. These observations suggest that DLGNT may in fact originate from an intramedullary lesion with a propensity for leptomeningeal dissemination.

over 1 year ago

Clinical • Epigenetic controller

BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR1 (Fibroblast growth factor receptor 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • SYP (Synaptophysin) • OLIG2 (Oligodendrocyte Transcription Factor 2)

BRAF V600E • FGFR1 mutation • MAP3K1 mutation • SETD2 mutation

over1year

Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes. (PubMed, Nat Commun)

Selective DNA methylation loss in CG-poor regions makes the chromatin accessible for alternative transcription. We show alternative promoters can control tumor transcriptomes and their regulatory architecture.

over 1 year ago

Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • DNMT3B (DNA Methyltransferase 3 Beta)

SETD2 mutation

over1year

Giant juvenile fibroadenomas with and without prominent pseudoangiomatous stromal hyperplasia (PASH)-like change: clinicopathological and molecular characteristics. (PubMed, Histopathology)

Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours.

over 1 year ago

Journal • Stroma

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • KMT2D (Lysine Methyltransferase 2D) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • BCOR (BCL6 Corepressor) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD34 (CD34 molecule) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)

TP53 mutation • RB1 mutation • TERT mutation • TERT promoter mutation • MAP3K1 mutation • PGR expression • SETD2 mutation • CTNNB1 expression • TERT 124C>T

over1year

Extensive intratumor regional epigenetic heterogeneity in clear cell renal cell carcinoma targets kidney enhancers and is associated with poor outcome. (PubMed, Clin Epigenetics)

Taken together, our results reveal marked levels of epigenetic ITH in ccRCC that are linked to clinically relevant tumor phenotypes and could translate into novel epigenetic biomarkers.

over 1 year ago

Journal

SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

SETD2 mutation