Disease relevance of MAML2

• Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)--associated TORC1-MAML2 gene fusion [1].
• Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin's tumors [2].
• CONCLUSIONS: Mammaglobin-A-derived peptide, MAM3, can induce mammaglobin-A-specific immunity and could be useful for vaccine strategies for patients with breast cancer [3].
• MAM-3 and MAM-6 antigens were detected immunohistochemically in 34 cases of adenoid cystic carcinomas (ACC) of the salivary glands and these patterns were compared to these of epithelial membrane antigen (EMA) and laminin [4].
• MAM-3 antigens, as detectable with monoclonals 67D11 and 115G3, were not detected in normal endometrial glands, but they were found in the majority of endometrial adenocarcinomas [5].

High impact information on MAML2

• MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product [6].
• Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation [7].
• In this report, we characterize two additional genes in this Mastermind-like gene family: MAML2 and MAML3 [8].
• In addition, the RNAi-specific vector had no effect on colony growth of non-MEC tumors including a lung tumor or two other salivary gland cell lines that do not express Mect1-Maml2 [9].
• In contrast, MAM3-specific T cell did not recognize wild type MDA415 or MDA415 transfected with HLA-A24, or the mammaglobin negative, HLA-A2 positive breast cancer cell line, MCF-7 [3].

Chemical compound and disease context of MAML2

• MAM-3 (MoAbs 115G3, 67D11) antigen was distributed in intercalated and striated duct cells of the normal salivary glands, and in luminal tumour cells and squamous metaplastic cells of pleomorphic adenomas [10].

Biological context of MAML2

• ISH analysis performed in cytogenetic suspension and/or in tumor paraffin sections demonstrated MAML2 rearrangement in 7 of 10 cases of MEC: all five cases with t(11;19), one case with normal karyotype, and one unkaryotyped case [11].
• Recent cloning of the MEC-1/MAML2 gene, resulting from translocations of chromosomes 11q21 and 19p23, has for the first time linked specific genetic alterations to the development of specific salivary gland tumors [12].
• Malignant salivary gland tumors can arise from a t(11;19) translocation that fuses 42 residues from Mect1/Torc1, a cyclic AMP (cAMP)/cAMP-responsive element binding protein (CREB)-dependent transcriptional coactivator, with 982 residues from Maml2, a NOTCH receptor coactivator [13].
• Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation [9].
• The immunohistochemical expression of MAM-3 and MAM-6 antigens was studied developing human fetal salivary gland removed at autopsy of 22 normal fetuses of varying maturity (10-40 weeks of gestation) [14].

Anatomical context of MAML2

• Two of the 7 peptides (MAM3 and MAM7) successfully induced peptide-specific T cells [3].
• Immunohistochemical localization of MAM-3 and MAM-6 antigens in adenoid cystic carcinoma [4].
• Myoepithelial derived tumor cells of ACC accompanying hyaline stroma demonstrated positive staining for the MAM-6 antigen (whole cell positive type), and luminal tumor cells of microcysts showed strong staining for the MAM-3 antigen [4].
• About 200 human tumours and corresponding normal tissue samples were investigated by immunoperoxidase tests for the expression of MAM-3, MAM-5 and MAM-6 antigens, which had previously been defined by monoclonal antibodies to human milk fat globule membranes [15].

Regulatory relationships of MAML2

• Here, we demonstrate that the MECT1-MAML2 fusion protein induces expression of multiple genes known to be CREB transcriptional targets [7].

References