Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

MAML2 (mastermind-like 2)

Written2003-07Goran Stenman
Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden
Updated2007-10Kazumi Suzukawa, Jean-Loup Huret
Department of Hematology, Institute of Clinical Medicine, University of Tsukuba (KS); Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH)

(Note : for Links provided by Atlas : click)


Other aliashMam-3
LocusID (NCBI) 84441
Atlas_Id 472
Location 11q21  [Link to chromosome band 11q21]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ACADL (2q34) / MAML2 (11q21)C11orf95 (11q13.1) / MAML2 (11q21)CHD6 (20q12) / MAML2 (11q21)
CRTC1 (19p13.11) / MAML2 (11q21)CRTC3 (15q26.1) / MAML2 (11q21)CXCR4 (2q22.1) / MAML2 (11q21)
KMT2A (11q23.3) / MAML2 (11q21)MALAT1 (11q13.1) / MAML2 (11q21)MAML2 (11q21) / CEP57 (11q21)
MAML2 (11q21) / CNTN5 (11q22.1)MAML2 (11q21) / CRTC1 (19p13.11)MAML2 (11q21) / CRTC3 (15q26.1)
MAML2 (11q21) / EPHB2 (1p36.12)MAML2 (11q21) / KMT2A (11q23.3)MAML2 (11q21) / MAML2 (11q21)
MAML2 (11q21) / MYO5A (15q21.2)MAML2 (11q21) / PATJ (1p31.3)MAML2 (11q21) / RTKN (2p13.1)
MTMR2 (11q21) / MAML2 (11q21)MYB (6q23.3) / MAML2 (11q21)TANC1 (2q24.2) / MAML2 (11q21)
YAP1 (11q22.1) / MAML2 (11q21)


Description Spans 365 kb; 5 exons.
Transcription A major transcript of 7.5 kb.


Description 1153 aa, 125 kDa; conserved N-terminal basic domain (aa 29-92) which binds to the ankyrin repeat domain of Notch receptors; two acidic domains (aa 263-360 and 1124-1153) and a C-terminal transcriptional activation domain.
Expression Widely expressed.
Localisation Nuclear granules.
Function Mastermind-like coactivator for all four Notch receptors; forms a complex with the Notch intracellular domain (Notch ICD) and the CSL family of transcription factors (CSL: CBF1/RBP-jk, Suppressor of Hairless, LAG1), resulting in activation of the Notch target genes HES1 and HES5; functions as a CSL-dependent transcriptional coactivator for ligand-stimulated Notch.
Homology MAML1 and MAML3.

Implicated in

Entity mucoepidermoid carcinoma with t(11;19)(q21-22;p13).
Disease - Most common type of malignant salivary gland tumor;
- Second most frequent lung tumor of bronchial gland origin;
- Rare tumour in the thyroid.
The t(11;19) was found in samples from the three different sites.
Prognosis - Mucoepidermoid carcinomas have an unpredictable behaviour.
- The CRTC1-MAML2 fusion transcript was found equally in low, intermediate and high grade tumours; however, tumours lacking the fusion transcript were significantly associated with metastases; they may represent a subset of aggressive tumours.
- In another study, the median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients.
Hybrid/Mutated Gene CRTC1-MAML2; exon 1 of CRTC1 fused to exons 2-5 of MAML2. Note: CRTC1 is also known as MECT1, or WAMTP1.
Abnormal Protein CRTC1-MAML2. In the fusion protein, the first 171 aa including the basic domain of MAML2 are replaced by 42 aa of CRTC1; there are no sequence similarities in the N-terminal domains of MAML2 and CRTC1. The fusion protein activates transcription of the Notch target gene HES1 independently of both Notch ligand and CSL.
Transforming activity of CRTC1-MAML2 fusion oncoprotein is mediated by mimicking constitutive activation of cAMP signaling, by activating CREB directly.
Entity Warthin's tumor with t(11;19)(q21-22;p13).
Note In rare instances mucoepidermoid carcinoma may arise from or coexist with Warthin's tumors.
Disease Warthin's tumor is a salivary gland neoplasm consisting of benign epithelial and lymphoid components; malignant transformation is extremely rare.
Hybrid/Mutated Gene CRTC1-MAML2
Entity Clear Cell Hidradenomas of the skin with t(11;19)(q21-22;p13)
Disease Clear Cell Hidradenomas of the skin are benign sweat gland tumors of eccrine duct origin.
Hybrid/Mutated Gene CRTC1-MAML2; exon 1 of CRTC1 fused to exons 2 of MAML2.
Entity inv(11)(q21q23) in therapy related leukemias
Disease therapy-related acute leukemia and MDS.
Hybrid/Mutated Gene MLL-MAML2; exon 1-7 of MLL fused to exons 2-5 of MAML2.
Abnormal Protein Hybrid transcript MLL/MAML2 contains the following domains: from MLL: AT-hook, DNA-Methyltransferase; from MAML2: Q rich domain, acidic domain.



To be noted

It is amazing that a similar fusion transcript (CRTC1-MAML2) can be seen both in a benign and in a malignant tumour of the same organ: Warthin's tumor, a benign salivary gland neoplasm, and mucoepidermoid carcinoma of the salivary gland: either another event differentiate the two, or the genetic event takes place in different cell types or in a given cell type at different states of differenciation.
It has been hypothezised that CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity.


Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
Behboudi A, Enlund F, Winnes M, Andrén Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, Mäkitie A, Grenman R, Mark J, Stenman G
Genes, chromosomes & cancer. 2006 ; 45 (5) : 470-481.
PMID 16444749
Translocation t(11;19)(q21;p13.1) as the sole chromosome abnormality in a cystadenolymphoma (Warthin's tumor) of the parotid gland.
Bullerdiek J, Haubrich J, Meyer K, Bartnitzke S
Cancer genetics and cytogenetics. 1988 ; 35 (1) : 129-132.
PMID 3180001
Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors.
Enlund F, Behboudi A, Andrén Y, Oberg C, Lendahl U, Mark J, Stenman G
Experimental cell research. 2004 ; 292 (1) : 21-28.
PMID 14720503
Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands.
Jhappan C, Gallahan D, Stahle C, Chu E, Smith GH, Merlino G, Callahan R
Genes & development. 1992 ; 6 (3) : 345-355.
PMID 1372276
Identification of new human mastermind proteins defines a family that consists of positive regulators for notch signaling.
Lin SE, Oyama T, Nagase T, Harigaya K, Kitagawa M
The Journal of biological chemistry. 2002 ; 277 (52) : 50612-50620.
PMID 12386158
Chromosomal patterns in Warthin's tumor. A second type of human benign salivary gland neoplasm.
Mark J, Dahlenfors R, Stenman G, Nordquist A
Cancer genetics and cytogenetics. 1990 ; 46 (1) : 35-39.
PMID 2331681
A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands.
Martins C, Cavaco B, Tonon G, Kaye FJ, Soares J, Fonseca I
The Journal of molecular diagnostics : JMD. 2004 ; 6 (3) : 205-210.
PMID 15269296
Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).
Nemoto N, Suzukawa K, Shimizu S, Shinagawa A, Takei N, Taki T, Hayashi Y, Kojima H, Kawakami Y, Nagasawa T
Genes, chromosomes & cancer. 2007 ; 46 (9) : 813-819.
PMID 17551948
Recurrent rearrangements of 11q14-22 in mucoepidermoid carcinoma.
Nordkvist A, Gustafsson H, Juberg-Ode M, Stenman G
Cancer genetics and cytogenetics. 1994 ; 74 (2) : 77-83.
PMID 8019965
A child with a t(11;19)(q14-21;p12) in a pulmonary mucoepidermoid carcinoma.
Stenman G, Petursdottir V, Mellgren G, Mark J
Virchows Archiv : an international journal of pathology. 1998 ; 433 (6) : 579-581.
PMID 9870694
CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: implications for histogenesis and biologic behavior.
Tirado Y, Williams MD, Hanna EY, Kaye FJ, Batsakis JG, El-Naggar AK
Genes, chromosomes & cancer. 2007 ; 46 (7) : 708-715.
PMID 17437281
t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.
Tonon G, Modi S, Wu L, Kubo A, Coxon AB, Komiya T, O'Neil K, Stover K, El-Naggar A, Griffin JD, Kirsch IR, Kaye FJ
Nature genetics. 2003 ; 33 (2) : 208-213.
PMID 12539049
Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas.
Winnes M, Mölne L, Suurküla M, Andrén Y, Persson F, Enlund F, Stenman G
Genes, chromosomes & cancer. 2007 ; 46 (6) : 559-563.
PMID 17334997
MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.
Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD
Nature genetics. 2000 ; 26 (4) : 484-489.
PMID 11101851
Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation.
Wu L, Liu J, Gao P, Nakamura M, Cao Y, Shen H, Griffin JD
The EMBO journal. 2005 ; 24 (13) : 2391-2402.
PMID 15961999
Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors.
Wu L, Sun T, Kobayashi K, Gao P, Griffin JD
Molecular and cellular biology. 2002 ; 22 (21) : 7688-7700.
PMID 12370315
Conservation of the Notch signalling pathway in mammalian neurogenesis.
de la Pompa JL, Wakeham A, Correia KM, Samper E, Brown S, Aguilera RJ, Nakano T, Honjo T, Mak TW, Rossant J, Conlon RA
Development (Cambridge, England). 1997 ; 124 (6) : 1139-1148.
PMID 9102301


This paper should be referenced as such :
Suzukawa, K ; Huret, JL
MAML2 (mastermind-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(3):220-222.
Free journal version : [ pdf ]   [ DOI ]
On line version :
History of this paper:
Stenman, G. MAML2 (mastermind-like 2). Atlas Genet Cytogenet Oncol Haematol. 2003;7(3):170-171.

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 6 ]
  inv(11)(q21q23) KMT2A/MAML2 in therapy related leukemias
t(2;11)(q22;q21) CXCR4/MAML2
inv(11)(q21q23)|t(11;11)(q21;q23) KMT2A/MAML2
inv(11)(q21q23) KMT2A/MAML2 in therapy related leukemias
t(2;11)(q22;q21) CXCR4/MAML2
inv(11)(q21q23)|t(11;11)(q21;q23) KMT2A/MAML2

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 10 ]
  Skin: Clear cell hidradenoma
Head and Neck: Salivary gland tumors: an overview
Head and Neck: Salivary gland tumors: Mucoepidermoid carcinoma with t(6;22)(p21;q12) EWSR1/POU5F1
t(6;11)(q23;q21) MYB/MAML2
t(11;11)(q21;q22) MAML2/CNTN5
t(11;11)(q21;q22) YAP1/MAML2
t(11;11)(q21;q22) YAP1/MAML2
t(11;15)(q21;q26) CRTC3/MAML2
t(11;19)(q21;p13) CRTC1/MAML2
Head and Neck: Salivary gland tumors: Warthin's tumors

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)84441
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 18 17:42:05 CEST 2018

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us