Affinage

MAML2

Mastermind-like protein 2 · UniProt Q8IZL2

Length
1156 aa
Mass
125.2 kDa
Annotated
2026-04-28
100 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAML2 is a transcriptional coactivator that participates in Notch/RBPJ-dependent transcription and, through recurrent chromosomal fusions, drives tumorigenesis in multiple tissue contexts. The CRTC1-MAML2 fusion, generated by t(11;19), constitutively recruits p300/CBP to CREB target genes via direct binding of MAML2's TAD1 domain to the CBP KIX domain, activating CREB-dependent transcription programs including AREG/EGFR autocrine signaling, LINC00473/NONO-mediated positive feedback, and PGC-1α4/IGF-1 circuits, and additionally co-opts MYC transcriptional activity to sustain transformation (PMID:15961999, PMID:26274502, PMID:23975434, PMID:25071166, PMID:29353885, PMID:33626346). YAP1-MAML2 fusions drive poromas, porocarcinomas, and meningioma-like tumors through Hippo-resistant, TEAD-dependent YAP transcriptional activity, with phase separation of the fusion selectively amplifying a subset of YAP target genes (PMID:31145701, PMID:36008139, PMID:38315854). A pathogenic MAML2 variant causes congenital hypothyroidism through dominant-negative disruption of Notch signaling and consequent loss of HES1-dependent thyroid hormone biosynthesis gene expression (PMID:36898841).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2004 High

    Identification of the t(11;19) CRTC1-MAML2 fusion established that MAML2's Notch ICD-binding basic domain is replaced in the chimera, raising the question of whether the oncogenic mechanism operates through Notch pathway disruption or a novel gain-of-function.

    Evidence Cloning, N-terminal mutagenesis, nuclear localization studies, and Notch target gene expression analysis in MEC tumors

    PMID:14720503

    Open questions at the time
    • Whether the fusion transforms through Notch pathway modulation or an independent mechanism was unresolved
    • No functional transformation assay was performed
  2. 2005 High

    Two independent studies converged to show that CRTC1-MAML2 transforms cells by constitutively activating CREB-dependent transcription via p300/CBP recruitment, not through Notch target gene activation, resolving the central mechanistic question.

    Evidence Co-immunoprecipitation, dominant-negative CREB blocking, in-frame deletion mutagenesis of CREB-binding domain, transformation assays, and genome-wide gene expression profiling across multiple cell lines

    PMID:15961999 PMID:16103063

    Open questions at the time
    • The structural basis for MAML2-mediated CBP/p300 recruitment was unknown
    • Downstream CREB target genes mediating transformation were not identified
  3. 2006 High

    RNAi knockdown with rescue demonstrated that sustained CRTC1-MAML2 expression is required for MEC cell growth, establishing oncogene addiction and validating the fusion as a therapeutic target.

    Evidence RNAi knockdown, colony formation assay, in vivo xenograft, rescue with siRNA-resistant mutant construct

    PMID:16652146

    Open questions at the time
    • No in vivo genetic model existed to prove the fusion is sufficient for tumor initiation
    • Specific downstream effectors mediating growth dependence were unknown
  4. 2013 High

    Identification of AREG as a direct CRTC1-MAML2/CREB transcriptional target that activates autocrine EGFR signaling revealed a druggable downstream effector pathway.

    Evidence RNAi, gene expression analysis, pharmacological EGFR inhibition, in vitro and in vivo xenograft models

    PMID:23975434

    Open questions at the time
    • Whether EGFR inhibition alone is sufficient for durable tumor regression was untested
    • Additional CREB target genes contributing to transformation remained uncharacterized
  5. 2014 High

    Discovery that CRTC1-MAML2 physically interacts with MYC and activates MYC transcriptional targets revealed a gain-of-function activity beyond CREB, expanding the oncogenic mechanism.

    Evidence Reciprocal co-immunoprecipitation, gene expression profiling, transformation assays with loss-of-interaction mutants in MEC cells

    PMID:25071166

    Open questions at the time
    • The domain on MAML2 mediating MYC interaction was not mapped
    • Relative contribution of MYC vs. CREB axis to in vivo tumorigenesis was unclear
  6. 2015 High

    Structural characterization of the MAML2 TAD1-KIX domain interaction provided the molecular basis for constitutive CBP/p300 recruitment, showing that a conserved ~20-residue segment forms an alpha-helix on the MLL1-binding surface of KIX.

    Evidence In vitro peptide-KIX binding assay, NMR structural analysis, sequence conservation analysis

    PMID:26274502

    Open questions at the time
    • Whether disrupting the TAD1-KIX interaction is therapeutically tractable was untested
    • Full-length MAML2 structural context was not determined
  7. 2018 High

    LINC00473 was identified as a top CRTC1-MAML2-induced lncRNA that binds NONO and creates a positive feedback loop amplifying CREB transcription, establishing a non-coding RNA layer in the oncogenic circuit.

    Evidence Gene expression profiling, RNAi, RNA immunoprecipitation, RNA in situ hybridization, in vivo xenograft loss-of-function

    PMID:29353885

    Open questions at the time
    • How NONO binding to LINC00473 mechanistically enhances CREB transcription was not determined
    • Whether LINC00473 functions in fusion-negative contexts was unknown
  8. 2019 High

    Discovery of recurrent YAP1-MAML2 fusions in poromas and porocarcinomas, with TEAD reporter activation and anchorage-independent growth, established a second major MAML2 fusion class operating through Hippo/YAP signaling.

    Evidence RNA sequencing, FISH, TEAD luciferase reporter assay, anchorage-independent growth assay

    PMID:31145701

    Open questions at the time
    • Whether the MAML2 portion contributes transcriptional activation function or merely stabilizes YAP was unknown
    • No in vivo tumor model existed for YAP1-MAML2
  9. 2021 High

    A conditional transgenic mouse model demonstrated that CRTC1-MAML2 expression is sufficient for MEC formation with 100% penetrance, and cooperating p16-CDK4/6-RB pathway alterations were identified, enabling rational combination therapy (erlotinib plus palbociclib).

    Evidence Cre-conditional transgenic mouse, inducible RNAi in xenografts, molecular pathway analysis, combination drug treatment in vitro and in vivo

    PMID:33830080

    Open questions at the time
    • Cell of origin for CRTC1-MAML2-driven MEC was not definitively established
    • Combination therapy efficacy in human patients was not tested
  10. 2021 High

    Identification of PGC-1α4 induction and autocrine IGF-1/IGF-1R signaling as a CRTC1-MAML2-driven vulnerability revealed an additional targetable downstream axis distinct from AREG/EGFR.

    Evidence Gene expression profiling, small-molecule drug screens, knockdown studies, IGF-1R inhibitor treatment in cell lines and primary tumors

    PMID:33626346

    Open questions at the time
    • Whether IGF-1R and EGFR inhibition are complementary or redundant was not resolved
    • The mechanism by which CRTC1-MAML2 selectively induces the PGC-1α4 isoform was unclear
  11. 2022 High

    In vivo mouse modeling showed YAP1-MAML2 drives meningioma-like tumors through Hippo-resistant TEAD-dependent YAP activity, and constitutively active YAP alone recapitulated tumorigenesis, clarifying that the MAML2 portion confers Hippo resistance rather than independent transcriptional coactivation.

    Evidence Mouse in vivo tumor induction, gene expression profiling, YAP-TEAD inhibitor treatment ex vivo, constitutively active YAP mutant expression

    PMID:36008139

    Open questions at the time
    • Whether MAML2's TAD contributes any transcriptional enhancement beyond Hippo evasion was not fully resolved
    • In vivo therapeutic efficacy of TEAD inhibitors was not tested
  12. 2023 Medium

    A pathogenic MAML2 variant was linked to congenital hypothyroidism by exerting a dominant-negative effect on Notch signaling, establishing the first Mendelian disease association and revealing that MAML2's Notch coactivator function is essential for HES1-dependent thyroid hormone biosynthesis.

    Evidence Next-generation sequencing, functional assays in HEK293T and thyroid cells, zebrafish and mouse models, organoid culture, transcriptome analysis

    PMID:36898841

    Open questions at the time
    • Single family study; independent replication in additional patients is needed
    • Whether other MAML family members compensate for MAML2 loss in thyroid was not addressed
  13. 2024 High

    YAP1-MAML2 undergoes phase separation forming transcriptionally active condensates, but chemogenetic dissolution showed that only a small subset of target genes (including CTGF, CYR61) require phase separation, while most targets are activated by diffuse TF complexes.

    Evidence Live imaging, FRAP, chemogenetic condensate dissolution tool, RNA-seq at matched protein levels

    PMID:38315854

    Open questions at the time
    • What distinguishes genes requiring phase separation from those that do not is unknown
    • Whether phase separation contributes to YAP1-MAML2 in vivo tumorigenesis was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the physiological (non-fusion) functions of wild-type MAML2 beyond Notch coactivation, the structural basis for MAML2-MYC interaction, and whether the TAD of MAML2 contributes transcriptional coactivation independently of the fusion partner in YAP1-MAML2-driven tumors.
  • Wild-type MAML2's non-Notch transcriptional roles are poorly characterized
  • No full-length MAML2 structure exists
  • Therapeutic strategies targeting MAML2 directly have not been developed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1643685 Disease 3
Partners
CREB1CREBBPEP300MYCNONORBPJTEAD1
Complex memberships
CRTC1-MAML2/CREB/p300 complexNotch transcription complex (RBPJ/NICD/MAML2)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 The t(11;19) translocation creates a WAMTP1-MAML2 (later called CRTC1-MAML2) fusion protein in which the N-terminal basic domain of MAML2 required for binding to intracellular Notch (Notch ICD) is replaced by an unrelated N-terminal sequence from WAMTP1. Mutation analysis identified two regions important for nuclear localization (amino acids 11-20) and colocalization with MAML2 and Notch1 ICD in nuclear granules (amino acids 21-42). The fusion results in upregulation of HES5 and downregulation of MASH1 in fusion-positive MECs, indicating altered Notch signaling. Cloning, mutation analysis of N-terminus, nuclear localization studies, Notch target gene expression analysis in MEC tumors Experimental cell research High 14720503
2005 The MECT1-MAML2 fusion protein binds to CREB, recruits p300/CBP into the CREB complex through a binding domain on MAML2, and constitutively activates CREB-dependent transcription. Blocking CREB DNA binding markedly reduced the transforming activity of MECT1-MAML2, demonstrating that constitutive CREB activation is the primary mechanism of transformation. Co-immunoprecipitation, luciferase reporter assays, dominant-negative CREB blocking, gene expression analysis, transformation assays The EMBO journal High 15961999
2005 Small in-frame deletions within the CREB-binding domain of Mect1/Torc1 portion of the Mect1-Maml2 fusion completely abolished transforming activity in RK3E epithelial cells. Ectopic induction of Mect1-Maml2 strongly activated known cAMP/CREB-regulated genes but did not alter known Notch-regulated target genes, establishing that cAMP/CREB pathway activation (not Notch signaling) is the primary oncogenic mechanism. In-frame deletion mutagenesis, doxycycline-regulated expression, global gene expression profiling, RT-PCR validation in multiple cell lines Cancer research High 16103063
2006 Sustained expression of Mect1-Maml2 is required for tumor cell growth in MEC cancer cells carrying the t(11;19) translocation. RNAi-mediated knockdown of the fusion peptide caused at least 90% colony growth inhibition in MEC cell lines, while having no effect on non-MEC tumors. A rescue experiment using a mutant Mect1-Maml2 with silent changes in the RNAi target sequence partially restored growth, confirming on-target specificity. RNAi knockdown, colony formation assay, in vivo xenograft, rescue experiment with RNAi-resistant mutant Oncogene High 16652146
2007 The CRTC1-MAML2 gene fusion is present in 50% of clear cell hidradenomas (benign skin tumors), demonstrating that the fusion's oncogenic activity extends beyond salivary and bronchial gland tumors. All fusion-positive hidradenomas had clear cell morphology, while all fusion-negative tumors lacked clear cells, establishing a genotype-phenotype correlation. FISH, RT-PCR, immunohistochemistry Genes, chromosomes & cancer Medium 17334997
2007 A novel MLL-MAML2 fusion gene is created by inv(11)(q21q23) in secondary AML/MDS. In the fusion, the N-terminal basic domain of MAML2 (including the Notch ICD binding site) is deleted. Luciferase assay demonstrated that MLL-MAML2 suppresses HES1 promoter activation by NOTCH1 intracellular domain, indicating dominant-negative disruption of Notch signaling. RT-PCR, sequencing, luciferase reporter assay for HES1 promoter Genes, chromosomes & cancer Medium 17551948
2013 CRTC1-MAML2 fusion oncogene is required for growth and survival of fusion-positive MEC cells in vitro and in vivo. The oncoprotein induces upregulation of the EGFR ligand Amphiregulin (AREG) by co-activating transcription factor CREB, and AREG subsequently activates EGFR signaling in an autocrine manner. CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR signaling inhibition. RNA interference, gene expression analysis, pharmacological EGFR inhibition, in vitro growth assays, in vivo xenograft models Oncogene High 23975434
2014 The CRTC1/MAML2 (C1/M2) oncoprotein interacts with MYC proteins and activates MYC transcription targets including genes involved in cell growth, metabolism, survival, and tumorigenesis. The C1/M2-MYC interaction is necessary for C1/M2-driven cell transformation, representing a gain-of-function activity beyond CREB and NOTCH pathway dysregulation. Co-immunoprecipitation, gene expression profiling, transformation assays in human MEC tumor cells with t(11;19) Proceedings of the National Academy of Sciences of the United States of America High 25071166
2015 A peptide derived from transactivation domain 1 (TAD1) of MAML2 binds directly to the CBP KIX domain with micromolar affinity. An ~20-residue segment within this peptide, conserved in MAML2 orthologs and paralogs, binds a KIX surface previously shown to bind MLL1, forming an alpha-helix similar to the MLL1-KIX interaction. Because CRTC1/3-MAML2 fusion proteins are constitutively nuclear, this provides the mechanism for constitutive CBP/p300 recruitment to CREB targets. In vitro binding assay (peptide-KIX domain), NMR structural analysis, sequence conservation analysis Biochemistry High 26274502
2016 Stilbenoids (resveratrol and pterostilbene) induce de novo methylation at the MAML2 enhancer, recruiting DNMT3B and reducing OCT1 transcription factor occupancy, leading to transcriptional silencing of MAML2 and downregulation of NOTCH target genes in breast cancer cells. Increased repressive histone marks and decreased activating marks accompany the enhanced DNA methylation. Genome-wide DNA methylation analysis (Illumina 450K), ChIP assay, immunohistochemistry, transcriptomics Carcinogenesis Medium 27207652
2018 CRTC1-MAML2 fusion induces transcription of the lncRNA LINC00473, which was the top downregulated target upon CRTC1-MAML2 depletion. LINC00473 induction requires CRTC1-MAML2's ability to activate CREB-mediated transcription. LINC00473 localizes predominantly to the nucleus and binds the cAMP signaling component NONO, enhancing CRTC1-MAML2-mediated CREB transcription in a positive feedback loop. LINC00473 depletion reduced MEC cell proliferation and blocked in vivo tumor growth. Gene expression profiling, RNA interference, RIP assay, RNA in situ hybridization, in vivo xenograft, loss-of-function studies Oncogene High 29353885
2019 YAP1-MAML2 fusions are highly recurrent in poromas (88.5%) and porocarcinomas (63.6%). The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic role through YAP/TEAD-dependent transcription. RNA sequencing, RT-PCR, FISH, TEAD reporter luciferase assay, anchorage-independent growth assay The Journal of clinical investigation High 31145701
2021 CRTC1-MAML2 is the major oncogenic driver of MEC in vivo: doxycycline-induced CRTC1-MAML2 knockdown blocked established MEC xenograft growth, and Cre-induced CRTC1-MAML2 expression in a conditional transgenic mouse model caused 100% penetrant salivary gland tumor formation resembling human MEC. Altered p16-CDK4/6-RB pathway activity was identified as a cooperating event, and cotargeting AREG/EGFR (erlotinib) and CDK4/6 (palbociclib) produced enhanced antitumor responses. Inducible RNAi knockdown in xenografts, conditional transgenic mouse model, molecular pathway analysis, combination drug treatment in vitro and in vivo JCI insight High 33830080
2021 CRTC1/MAML2 (C1/M2) induces transcriptional activation of the non-canonical PGC-1α splice variant PGC-1α4, which drives PPARγ-mediated IGF-1 expression in an autocrine circuit. C1/M2-positive MEC cells are selectively sensitive to IGF-1R inhibition and PPARγ inverse agonists, revealing a PGC-1α-IGF-1 signaling axis as a vulnerability in fusion-positive tumors. Gene expression profiling, small-molecule drug screens, knockdown studies, IGF-1R inhibitor treatment in cell lines and primary tumors Cell reports High 33626346
2021 LINC01152 positively regulates MAML2 in GBM cells by sponging miR-466 and by recruiting SRSF1. In turn, the RBPJ/MAML2 transcription complex activates transcription of LINC01152, forming a positive feedback loop that promotes GBM tumorigenesis via the Notch signaling pathway. RNA pulldown assay, luciferase reporter assay, RIP assay, ChIP assay, functional proliferation/apoptosis assays Cell death & disease Medium 33483471
2022 YAP1-MAML2 primarily functions by exerting TEAD-dependent YAP activity that is resistant to Hippo signaling. Expression of YAP1-MAML2 in mice induces meningioma-like tumors resembling NF2 mutant meningiomas by gene expression. Treatment with YAP-TEAD inhibitors is sufficient to inhibit viability of YAP1-MAML2-driven mouse tumors ex vivo. Constitutively active YAP1 (S127/397A-YAP1) alone is sufficient to induce similar tumors, establishing that the YAP component drives oncogenesis. Mouse in vivo tumor induction, gene expression profiling, YAP-TEAD inhibitor treatment ex vivo, constitutively active YAP1 mutant expression Genes & development High 36008139
2023 A pathogenic MAML2 variant was identified in a patient with congenital hypothyroidism due to dyshormonogenesis. The MAML2 variant exerted a dominant-negative effect on canonical Notch signaling and on thyroid hormone biosynthesis. In zebrafish and mouse models, Notch pathway inhibition (γ-secretase inhibitor) recapitulated hypothyroidism and dyshormonogenesis. HES1, a Notch target transactivated by MAML2, directly regulates thyroid hormone biosynthesis gene expression. Next-generation sequencing, in vitro functional assays in HEK293T and Nthy-ori 3.1 cells, zebrafish and mouse models, organoid culture, transcriptome sequencing Journal of medical genetics Medium 36898841
2024 YAP1-MAML2 undergoes phase separation and forms liquid-like condensates bearing hallmarks of transcriptional activity. Using a chemogenetic tool to dissolve TF condensates, phase separation was found to further upregulate a small fraction of YAP1-MAML2-regulated genes (including canonical YAP targets CTGF and CYR61) while the majority of YAP1-MAML2-regulated genes are not affected by phase separation, indicating that diffuse TF complexes can activate transcription without phase separation. Phase separation assays (live imaging, FRAP), chemogenetic dissolution of condensates, RNA-seq comparison of phase-separated vs. non-phase-separated conditions at identical protein levels Proceedings of the National Academy of Sciences of the United States of America High 38315854

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. The American journal of surgical pathology 209 20588178
2019 Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma. The Journal of clinical investigation 198 31145701
2006 MECT1-MAML2 fusion transcript defines a favorable subset of mucoepidermoid carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 169 16818685
2007 MAM3 catalyzes the formation of all aliphatic glucosinolate chain lengths in Arabidopsis. Plant physiology 136 17369439
2009 Clinicopathological significance of the CRTC3-MAML2 fusion transcript in mucoepidermoid carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 133 19749740
2005 Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. The EMBO journal 121 15961999
2004 Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors. Experimental cell research 117 14720503
2005 Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes. Cancer research 112 16103063
2004 A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands. The Journal of molecular diagnostics : JMD 103 15269296
2018 MAML2 Rearrangements in Variant Forms of Mucoepidermoid Carcinoma: Ancillary Diagnostic Testing for the Ciliated and Warthin-like Variants. The American journal of surgical pathology 90 28877061
2008 A new type of MAML2 fusion in mucoepidermoid carcinoma. Genes, chromosomes & cancer 86 18050304
2007 Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas. Genes, chromosomes & cancer 82 17334997
2016 Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity. Carcinogenesis 81 27207652
2011 Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test. Human pathology 80 21777943
2005 Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion. Genes, chromosomes & cancer 79 15729701
2008 t(11;19) translocation and CRTC1-MAML2 fusion oncogene in mucoepidermoid carcinoma. Oral oncology 76 18486532
2013 Aberrantly activated AREG-EGFR signaling is required for the growth and survival of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells. Oncogene 74 23975434
2006 Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Oncogene 65 16652146
2019 Metaplastic thymoma: a distinctive thymic neoplasm characterized by YAP1-MAML2 gene fusions. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 63 31641231
2017 Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid carcinoma. Oral oncology 61 28438292
2020 Recurrent YAP1 and MAML2 Gene Rearrangements in Retiform and Composite Hemangioendothelioma. The American journal of surgical pathology 60 32991341
2021 The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma. JCI insight 59 33830080
2012 Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma. Cancer science 56 23035786
2008 CRTC1/MAML2 fusion transcript in Warthin's tumor and mucoepidermoid carcinoma: evidence for a common genetic association. Genes, chromosomes & cancer 53 18181164
2009 Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion. The American journal of surgical pathology 49 19092631
2018 CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells. Oncogene 45 29353885
2013 HER2 and EGFR gene copy number alterations are predominant in high-grade salivary mucoepidermoid carcinoma irrespective of MAML2 fusion status. Histopathology 41 23855785
2007 Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23). Genes, chromosomes & cancer 41 17551948
2018 CRTC1-MAML2 fusion in mucoepidermoid carcinoma of the breast. Histopathology 40 30380176
2022 Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2 mutant meningiomas in mice. Genes & development 38 36008139
2013 CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands. The American journal of surgical pathology 37 24121173
2009 Gefitinib as targeted therapy for mucoepidermoid carcinoma of the lung: possible significance of CRTC1-MAML2 oncogene. Lung cancer (Amsterdam, Netherlands) 37 19185385
2020 Pan-Cancer Landscape Analysis Reveals Recurrent KMT2A-MAML2 Gene Fusion in Aggressive Histologic Subtypes of Thymoma. JCO precision oncology 36 32923872
2016 Reevaluation of MAML2 fusion-negative mucoepidermoid carcinoma: a subgroup being actually hyalinizing clear cell carcinoma of the salivary gland with EWSR1 translocation. Human pathology 36 27769871
2017 A novel fusion gene CRTC3-MAML2 in hidradenoma: histopathological significance. Human pathology 33 29079171
2022 Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours. Histopathology 32 36208053
2014 CRTC1/MAML2 gain-of-function interactions with MYC create a gene signature predictive of cancers with CREB-MYC involvement. Proceedings of the National Academy of Sciences of the United States of America 30 25071166
2013 Analysis of MAML2 rearrangement in mucoepidermoid carcinoma of the thymus. Human pathology 30 24134933
2021 Mucoepidermoid carcinoma of the salivary glands revisited with special reference to histologic grading and CRTC1/3-MAML2 genotyping. Virchows Archiv : an international journal of pathology 29 34231055
2010 CRTC1/MAML2 fusion transcript in central mucoepidermoid carcinoma of mandible--diagnostic and histogenetic implications. Annals of diagnostic pathology 28 21074686
2021 Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features. Histopathology 27 34657306
2016 Cutaneous hidradenoma: a study of 21 neoplasms revealing neither correlation between the cellular composition and CRTC1-MAML2 fusions nor presence of CRTC3-MAML2 fusions. Annals of diagnostic pathology 27 27402217
2022 Recurrent YAP1::MAML2 fusions in "nodular necrotizing" variants of myxoinflammatory fibroblastic sarcoma: a comprehensive study of 7 cases. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26 35546636
2021 YAP1-MAML2 Fusion as a Diagnostic Biomarker for Metaplastic Thymoma. Frontiers in oncology 26 34354947
2021 LINC01152 upregulates MAML2 expression to modulate the progression of glioblastoma multiforme via Notch signaling pathway. Cell death & disease 25 33483471
2012 Expression pattern of the glucosinolate side chain biosynthetic genes MAM1 and MAM3 of Arabidopsis thaliana in different organs and developmental stages. Plant physiology and biochemistry : PPB 24 22336876
2022 CircRNA_Maml2 promotes the proliferation and migration of intestinal epithelial cells after severe burns by regulating the miR-93-3p/FZD7/Wnt/β-catenin pathway. Burns & trauma 23 35265724
2014 Mucoepidermoid carcinoma does not harbor transcriptionally active high risk human papillomavirus even in the absence of the MAML2 translocation. Head and neck pathology 23 24706055
2014 MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression. PloS one 23 24714697
2015 Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 22 25953768
2015 A clear cell variant of mucoepidermoid carcinoma harboring CRTC1-MAML2 fusion gene found in buccal mucosa: report of a case showing a large clear cell component and lacking typical epidermoid cells and intermediate cells. Medical molecular morphology 22 26297211
2012 CRTC1-MAML2 gene fusion in mucoepidermoid carcinoma of the lacrimal gland. Oncology reports 21 22323114
1987 Immunohistochemical demonstration of MAM-3 and MAM-6 antigens in normal human skin appendages and their tumors. Archives of dermatological research 21 3435182
2010 Central mucoepidermoid carcinoma, a case report with molecular analysis of the TORC1/MAML2 gene fusion. Head and neck pathology 20 20625861
2022 MAML2 Gene Rearrangement Occurs in Nearly All Hidradenomas: A Reappraisal in a Series of 20 Cases. The American Journal of dermatopathology 19 35925563
2020 YAP1-MAML2-Rearranged Poroid Squamous Cell Carcinoma (Squamoid Porocarcinoma) Presenting as a Primary Parotid Gland Tumor. Head and neck pathology 18 32504288
2011 Oncocytic mucoepidermoid carcinoma of the parotid gland with CRTC1-MAML2 fusion transcript: report of a case with review of literature. Human pathology 18 21676434
2024 Phase separation of YAP-MAML2 differentially regulates the transcriptome. Proceedings of the National Academy of Sciences of the United States of America 17 38315854
2023 Malignant undifferentiated epithelioid neoplasms with MAML2 rearrangements: A clinicopathologic study of seven cases demonstrating a heterogenous entity. Genes, chromosomes & cancer 17 36344258
2022 Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma. International journal of molecular sciences 17 35457138
2020 Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma. Histopathology 17 32129900
2020 Ependymoma with C11orf95-MAML2 fusion: presenting with granular cell and ganglion cell features. Brain tumor pathology 16 33221956
2017 First case of B ALL with KMT2A-MAML2 rearrangement: a case report. BMC cancer 16 28535805
2015 Fluorescence in-situ hybridization identifies Mastermind-like 2 (MAML2) rearrangement in odontogenic cysts with mucous prosoplasia: a pilot study. Histopathology 16 25123064
2017 Spindle Cell Mucoepidermoid Carcinoma of the Palatine Tonsil With CRTC1-MAML2 Fusion Transcript: Report of a Rare Case in a 17-Year-Old Boy and a Review of the Literature. International journal of surgical pathology 15 28637362
2021 CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition. Cell reports 14 33626346
2020 Clear cell papillary neoplasm of the breast with MAML2 gene rearrangement: Clear cell hidradenoma or low-grade mucoepidermoid carcinoma? Pathology, research and practice 14 32853960
2019 Primary mucoepidermoid carcinoma of the liver with CRTC1-MAML2 fusion: a case report. Diagnostic pathology 14 31351495
2017 Assessment of biologically aggressive, recurrent glandular odontogenic cysts for mastermind-like 2 (MAML2) rearrangements: histopathologic and fluorescent in situ hybridization (FISH) findings in 11 cases. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 14 29121421
2017 Central mucoepidermoid carcinoma arising from glandular odontogenic cyst confirmed by analysis of MAML2 rearrangement: A case report. Pathology international 14 29131467
2012 MAML2 rearrangement in Warthin's tumour: a fluorescent in situ hybridisation study of metaplastic variants. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 14 22582766
1985 Expression of MAM-3 and MAM-6 antigens in endometrial and endocervical adenocarcinomas. Virchows Archiv. A, Pathological anatomy and histopathology 14 3925626
2018 The reliability of MAML2 gene rearrangement in discriminating between histologically similar glandular odontogenic cysts and intraosseous mucoepidermoid carcinomas. Oral surgery, oral medicine, oral pathology and oral radiology 13 30692056
2014 Translocation t(2;11) in CLL cells results in CXCR4/MAML2 fusion oncogene. Blood 13 24855209
2023 Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement. Head and neck pathology 12 36849671
2021 Reevaluation of Salivary Lymphadenoma: A Subgroup Identified as Warthin-like Mucoepidermoid Carcinoma Following Molecular Investigation for MAML2 Rearrangement. Archives of pathology & laboratory medicine 12 32960941
2009 A link between the expression of the stem cell marker HMGA2, grading, and the fusion CRTC1-MAML2 in mucoepidermoid carcinoma. Genes, chromosomes & cancer 12 19521953
2018 "Pancreatic Mucoepidermoid Carcinoma" Is not a Pancreatic Counterpart of CRTC1/3-MAML2 Fusion Gene-related Mucoepidermoid Carcinoma of the Salivary Gland, and May More Appropriately be Termed Pancreatic Adenosquamous Carcinoma With Mucoepidermoid Carcinoma-like Features. The American journal of surgical pathology 11 30138216
2015 Molecular Basis for the Mechanism of Constitutive CBP/p300 Coactivator Recruitment by CRTC1-MAML2 and Its Implications in cAMP Signaling. Biochemistry 11 26274502
2021 Adenocarcinoma of the minor salivary gland with concurrent MAML2 and EWSR1 alterations. Journal of pathology and translational medicine 10 33472334
2021 Whole Exome Sequencing Identifies Somatic Variants in an Oral Composite Hemangioendothelioma Characterized by YAP1-MAML2 Fusion. Head and neck pathology 10 34791601
2019 High Grade Transformation in Mucoepidermoid Carcinoma of the Minor Salivary Gland with Polyploidy of the Rearranged MAML2 Gene. Head and neck pathology 10 31535311
2009 Chromosomal imbalances, 11q21 rearrangement and MECT1-MAML2 fusion transcript in mucoepidermoid carcinomas of the salivary gland. Oncology reports 10 19578770
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2022 Establishment of a patient-derived mucoepidermoid carcinoma cell line with the CRTC1-MAML2 fusion gene. Molecular and clinical oncology 9 35251626
2017 Mucoepidermoid carcinoma of the sublingual gland harboring a translocation of the MAML2 gene: A case report. Oncology letters 9 28927048
2017 Sclerosing Mucoepidermoid Carcinoma in the Parotid Gland With CRTC1-MAML2 Fusion: A Case Report. International journal of surgical pathology 9 29169286
1989 Immunohistochemical expression of MAM-3 and MAM-6 antigens in salivary gland tumours. Virchows Archiv. A, Pathological anatomy and histopathology 9 2508309
2023 Atypical Intraparenchymal Meningioma with YAP1-MAML2 Fusion in a Young Adult Male: A Case Report and Mini Literature Review. International journal of molecular sciences 8 37628996
2022 Diagnostic Reliability of CRTC1/3::MAML2 Gene Fusion Transcripts in Discriminating Histologically Similar Intraosseous Mucoepidermoid Carcinoma from Glandular Odontogenic Cyst: A Systematic Review and Meta-analysis. Head and neck pathology 8 36357765
2024 MAML2 gene rearrangement occurs in all Warthin-like mucoepidermoid carcinoma: A reappraisal in a series of 29 cases. Heliyon 6 38304779
2023 Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway. Journal of medical genetics 6 36898841
2022 YAP1-MAML2 fusion in a pediatric NF2-wildtype intraparenchymal brainstem schwannoma. Acta neuropathologica communications 6 35986430
2022 Pediatric meningioma with a Novel MAML2-YAP1 fusion variant: a case report and literature review. BMC pediatrics 6 36463108
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2021 The Multifaceted Appearance of Supratentorial Ependymoma with ZFTA-MAML2 Fusion. Free neuropathology 5 37284641
2020 Inv(11)(q21q23); KMT2A-MAML2, a Recurrent Genetic Abnormality in T-Cell Therapy-related Acute Lymphoblastic Leukemia. Journal of pediatric hematology/oncology 5 31343482
2020 Ameloblastoma with mucous cells: A clinicopathological, BRAF mutation, and MAML2 rearrangement study. Oral diseases 4 31954088
2019 Gefitinib Represses JAK-STAT Signaling Activated by CRTC1-MAML2 Fusion in Mucoepidermoid Carcinoma Cells. Current cancer drug targets 4 30605061