Daxx
- Known as:
- Daxx
- Catalog number:
- 11-351-C100
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- Exbio
- Gene target:
- Daxx
Related genes to: Daxx
- Gene:
- DAXX NIH gene
- Name:
- death domain associated protein
- Previous symbol:
- -
- Synonyms:
- DAP6
- Chromosome:
- 6p21.32
- Locus Type:
- gene with protein product
- Date approved:
- 1998-03-25
- Date modifiied:
- 2016-10-05
Related products to: Daxx
Related articles to: Daxx
- Alterations in alternative splicing are emerging as a novel cancer hallmark, offering new insights into tumor biology. However, integrative analyses of splicing are still scarce, particularly in rare cancers like pancreatic neuroendocrine tumors (PanNETs), whose striking heterogeneity complicates patient diagnosis and treatment. Here, we provide the first comprehensive characterization of the RNA splicing landscape in PanNETs through integrative analysis of RNA-seq data from 174 tumor samples. We identified three robust spliceosomic groups (SPN1, SPN2, SPN3) each associated with unique clinical and molecular characteristics. SPN1 displayed intermediate clinical behavior alongside enhanced mTOR signaling; SPN2 was characterized by a less secretory phenotype, enrichment in alpha-cell markers and somatostatin receptors, increased metastasis, and frequent mutations in MEN1 and DAXX/ATRX genes; in contrast, SPN3 was composed mainly by low grade tumors with beta-cell marker expression and the lowest mutational rate, yet it also contained all the highly proliferative neoplasms. Moreover, each group had a specific alternative splicing events signature, revealing an unprecedented discovery: the association between the expression profile of the splicing machinery and its product, the splicing variants. We provide a detailed characterization of the molecular and functional consequences of the splice variants defining each of the spliceosomic groups. These findings underscore the previously unrecognized yet significant impact of RNA splicing on PanNET heterogeneity and suggest that detailed splicing profiles could serve as valuable tools for identifying novel biomarkers and therapeutic targets. Thus, beyond providing crucial insights into PanNET molecular biology, our study offers a foundation for future studies exploring personalized therapeutic strategies based on splicing features. - Source: PubMed
Publication date: 2026/07/09
Blázquez-Encinas RicardoGarcía-Vioque VíctorMafficini AndreaLandoni LucaRuiz-Palacios DanielGutiérrez-Camacho LauraMoreno-Montilla María TrinidadAlcala NicolasVentura SebastiánEyras EduardoPaiella SalvatoreSalvia RobertoRovite VitaFoll MatthieuLuchini ClaudioFernandez-Cuesta LynnetteLawlor Rita TScarpa AldoIbáñez-Costa AlejandroPedraza-Arevalo SergioCastaño Justo P - Mutations in the ATRX chromatin remodeler confer a predisposition to a developmental genetic disorder and cancer, but how ATRX safeguards genome and telomere stability remains unresolved. Here, we uncover critical dependencies for the CTC1-STN1-TEN1 (CST) complex and RAD9A-HUS1-RAD1 (9-1-1) clamp in ATRX-deficient cells. ATRX-CST synthetic lethality manifests following accumulation of telomeric G-rich single-stranded DNA (ssDNA), which results in telomere loss and cell death. Conversely, we attribute ATRX-9-1-1 synthetic lethality to genome-wide ssDNA lesions, which compromise DNA replication. We further show that ATRX suppresses DNA damage during replication stress by counteracting the activity of the FAM111A protease. We demonstrate that roles of ATRX in telomere maintenance and replication are genetically separable, requiring its ATPase activity and PIP-box, respectively. We also show that such roles protecting genome stability are largely independent of the ATRX-DAXX interaction. Collectively, our data show that functions of ATRX in suppressing toxic ssDNA lesions are context-dependent and are key to global DNA replication and telomere integrity. - Source: PubMed
Publication date: 2026/06/30
Segura-Bayona SandraMaric MarijaTakaki TohruManova ZornitsaStanage Tyler HIdilli Aurora ILi ShudongHewitt GraemeMachour Feras EMillar RhonaAdamowicz MarekLow Ronnie Ren JieRuis PhilAzeroglu BenuraFallesen ToddPatel HarshilHowell StevenKotsantis PanagiotisHowell MichaelBoulton Simon J - Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies ranging from relatively indolent well-differentiated neuroendocrine tumors (NETs) to more aggressive poorly differentiated neuroendocrine carcinomas (NECs). The advent of somatostatin receptor (SSTR)-targeting therapies, particularly radioligand therapy (RLT), has transformed the therapeutic landscape of NETs. Ongoing efforts are aimed at maximizing the therapeutic benefit of RLT and include retreatment and combination strategies as well as novel α-emitter-based radiopharmaceuticals. The increasing use of molecular profiling has led to the identification of recurrent canonical alterations in pancreatic NETs, including in , /, PI3K/Akt/mTOR, and angiogenic signaling pathways, facilitating the development of effective targeted therapies. However, despite the addition of newer targeted therapies to the therapeutic armamentarium, resistance remains inevitable and highlights the need for improved predictive markers to inform therapy sequencing and novel biomarker-selected therapies. In addition, the development of novel therapeutic strategies including SSTR antagonists, nonpeptide drug conjugates, and novel radiopharmaceutical constructs highlights the potential of biomarker-informed therapies in this space. By contrast, treatment options for NECs remain limited, with modest therapeutic benefit of platinum-based chemotherapy. The identification of delta-like ligand 3 (DLL3) as a therapeutic target in high-grade NENs has led to the development of novel targeted therapies such as T-cell engagers, which have demonstrated promising activity in early phase clinical trials. In addition, other DLL3-targeting agents such as antibody-drug conjugates, trispecific engagers, and cellular therapies remain under investigation. Collectively, these advances underscore the potential of biomarker-informed treatment approaches to personalize treatment decisions and improve long-term outcomes across the NEN spectrum. - Source: PubMed
Publication date: 2026/06/26
Grewal Udhayvir SShaheen ShaguftaZhen David BMittra Erik SHalfdanarson Thorvardur RSingh SimronChan Jennifer A - Neuroendocrine carcinomas of the gallbladder (GBNECs) have been very poorly characterized. In this study, 31 NECs were identified through an analysis of 636 GB cancers and contrasted with the ordinary GBCs (O-GBCs) in the same cohort. Seven were pure small cell NECs, 2 pure large cell, and 22 had mixed adenocarcinoma component (with NEC component being small cell in 6 and large cell in 16). High-grade glandular dysplasia was evident in 15 (6 as intracholecystic neoplasms; vs. 6% in O-GBC), F:M ratio was 5.2:1, and median age was 58 (vs. 65 in O-GBC). The average neuroendocrine component constituted 80% of the tumor; the median Ki-67 was 70%; lymph-vascular invasion was seen in 74%, and perineural invasion in 56%. GBNECs presented with more advanced tumors; 72% were pT3/T4 (vs. 26% in O-GBC, P=0.001). Lymph node metastasis was in 5/10 (with lymph nodes available in the specimen), and 5 had distant metastases. Tumor cells were positive for neuroendocrine markers (synaptophysin 95%, chromogranin 75%, CD56 90%), keratins (AE1/3 90%, Cam5.2 88%), with upper-GI profile (CK7 65%; CK20 0%); TTF-1 in 25%. pRB loss was detected in 67%, positive p16 83%, mutant p53 88.8%, and SMAD4 loss in 24%. Overall, the pRB/p16 pathway was inactivated in 83% (12 [67%] as pRB loss/p16+, and 3 [17%] as pRB+/p16- ). DAXX was retained in all. Loss of pRB and p16 was also detected in about a third of the adenocarcinoma and preinvasive components. ATRX loss was noted in 1 large-cell NEC. The median survival was 6.1 months, significantly shorter than O-GBCs, although a few survived unexpectedly longer. Factors associated with shorter survival included pT3 versus pT2 stage, and a trend for lower synaptophysin and CD56 expression. In conclusion, NECs constitute <5% of GBCs, and two-thirds are admixed with an adenocarcinoma component. A fifth arises in intracholecystic neoplasms. Inactivation of the pRB/p16 pathway is common, with 2/3 showing pRB loss. They present as advanced tumors and behave aggressively. - Source: PubMed
Publication date: 2026/06/24
Reid Michelle DPehlivanoglu BurcinMemis BaharRoa Juan CMuraki TakashiKoshiol JillLicitra GiancarloGoodman MichaelAraya Juan CVillaseca MiguelLosada HectorSarmiento Juan MDursun NevraBasturk OlcaAdsay Volkan - The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent telomere maintenance mechanism, which is frequently observed in osteosarcoma. In this study, we performed a systematic review of studies assessing ALT in patient-derived osteosarcoma samples using direct experimental assays, alongside bioinformatic analysis of large public genomic datasets to evaluate the prevalence of canonical ALT-associated alterations. Across seven eligible studies comprising 342 tumours, ALT activity was identified in 62.9% of cases. In contrast, analysis of the Target-OS and PeCan datasets demonstrated that mutations in ATRX or DAXX, and amplification of TOP3A, occur at substantially lower frequencies, collectively accounting for only a minority of tumours. Statistical comparison confirmed a significant discrepancy between experimentally-observed ALT prevalence and the frequency of these canonical ALT-associated genetic alterations. These findings indicate that canonical genomic events are insufficient to explain ALT activation in osteosarcoma and support a model of marked biological heterogeneity. Potential alternative mechanisms include non-mutational disruption of chromatin remodelling pathways, replication stress-associated processes, and epigenetic dysregulation. The data highlights the limitations of relying on sequencing-based approaches alone to infer telomere maintenance mechanisms, which could have important clinical consequences for potential ALT-pathway targeting therapies. In conclusion, ALT is highly prevalent in osteosarcoma but is not adequately captured by known genetic correlates. Functional assays remain essential for accurate classification, and improved understanding of non-canonical ALT drivers will be critical for biomarker development and the design of targeted therapeutic strategies. - Source: PubMed
Publication date: 2026/06/02
Goncalves TomasMattis Natalie SMitchell Amy F MRose Anna M