Atlas of Genetics and Cytogenetics in Oncology and Haematology
MAML2 (mastermind-like 2)
| Identity |
| Other names | hMam-3 |
| KIAA1819 | |
| HGNC (Hugo) | MAML2 |
| LocusID (NCBI) | 84441 |
| Location | 11q21 |
| Location_base_pair | Starts at 95711440 and ends at 96076344 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| DNA/RNA |
| Description | Spans 365 kb; 5 exons. |
| Transcription | A major transcript of 7.5 kb. |
| Protein |
| 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. |
 | |
| Breakpoints |
 | |
| 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. |
| External links |
| Bibliography |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors. |
| Enlund F, Behboudi A, AndrŠn Y, Oberg C, Lendahl U, Mark J, Stenman G |
| Experimental cell research. 2004 ; 292 (1) : 21-28. |
| PMID 14720503 |
| 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 |
| Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion. |
| Behboudi A, Winnes M, Gorunova L, van den Oord JJ, Mertens F, Enlund F, Stenman G |
| Genes, chromosomes & cancer. 2005 ; 43 (2) : 202-205. |
| PMID 15729701 |
| 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 |
| Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene. |
| Behboudi A, Enlund F, Winnes M, AndrŠn Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, M§kitie A, Grenman R, Mark J, Stenman G |
| Genes, chromosomes & cancer. 2006 ; 45 (5) : 470-481. |
| PMID 16444749 |
| 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 |
| 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 |
| Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas. |
| Winnes M, Mlne L, Suurkēla M, AndrŠn Y, Persson F, Enlund F, Stenman G |
| Genes, chromosomes & cancer. 2007 ; 46 (6) : 559-563. |
| PMID 17334997 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 07-2003 | Goran Stenman |
| Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden | ||
| Updated | 10-2007 | Kazumi 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) |
| Citation |
| This paper should be referenced as such : |
| Stenman G . MAML2 (mastermind-like 2). Atlas Genet Cytogenet Oncol Haematol. July 2003 . URL : http://AtlasGeneticsOncology.org/Genes/MAML2ID472.html |
| Suzukawa K, Huret JL . MAML2 (mastermind-like 2). Atlas Genet Cytogenet Oncol Haematol. October 2007 . URL : http://AtlasGeneticsOncology.org/Genes/MAML2ID472.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/37983/1/07-2003-MAML2ID472.pdf [ Bibliographic record ] |
| http://documents.irevues.inist.fr/bitstream/2042/38524/1/10-2007-MAML2ID472.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 13:12:13 CEST 2013 |
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