Home > A. Molecular pathology > Fusion genes > MAML2-MECT1

MAML2-MECT1

Monday 8 March 2004

Definition: Fusion of the CREB regulated transcription coactivator MECT1 (a.k.a. CRTC1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas of salivary and bronchial glands.

The MECT1-MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein.

Pathology

- MECT1/MAML2 gene fusion in

  • mucoepidermoid carcinoma by t(11;19)(q21-22;p13) translocation (#14720503#)
  • benign Warthin tumor by t(11;19)(q21-22;p13) translocation (#14720503#)
  • clear cell hidradenoma

- mucoepidermoid carcinoma

  • The MECT1-MAML2 translocation is identified in a large proportion of mucoepidermoid carcinomas (MEC) of the salivary gland.
  • It is an emerging favorable prognostic factor.
  • -* The MECT1-MAML2 translocation is highly specific for MEC and imparts a better prognosis.
  • However, it is frequent even within high-grade MEC and can be seen in lethal cases suggesting that translocation status should not supersede conventional parameters. (#20588178#)
  • There are 2 distinct subgroups within high-grade MEC, and the translocation negative tumors may actually be more appropriately categorized as another tumor type (such as adenosquamous carcinoma). (#20588178#)

Action

- In the fusion protein, the N-terminal basic domain of MAML2, which is required for binding to intracellular Notch (Notch ICD), is replaced by an unrelated N-terminal sequence from WAMTP1.

- Mutation analysis of the N-terminus of WAMTP1-MAML2 identified two regions of importance for nuclear localization (amino acids 11-20) and for colocalization with MAML2 and Notch1 ICD in nuclear granules (amino acids 21-42).

- altered Notch signaling pathway with upregulation of HES5 and downregulation of MASH1(#14720503#)

- CRTC1-MAML2 and CRTC3-MAML2 Fusions are not detected in metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands.

References

- CRTC1-MAML2 and CRTC3-MAML2 Fusions Were Not Detected in Metaplastic Warthin Tumor and Metaplastic Pleomorphic Adenoma of Salivary Glands. 2013. doi:10.1097/PAS.0000000000000065

- A Reappraisal of the MECT1/MAML2 Translocation in Salivary Mucoepidermoid Carcinomas. Seethala RR, Dacic S, Cieply K, Kelly LM, Nikiforova MN. Am J Surg Pathol. Aug;34(8):1106-21. PMID: #20588178#

- Tirado Y, Williams MD, Hanna EY, Kaye FJ, Batsakis JG, El-Naggar AK. CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin’s tumors: implications for histogenesis and biologic behavior. Genes Chromosomes Cancer. 2007 Jul;46(7):708-15. PMID: #17437281#

- Winnes M, Molne L, Suurkula M, Andren Y, Persson F, Enlund F, Stenman G. Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas. Genes Chromosomes Cancer. 2007 Jun;46(6):559-63. PMID: #17334997#

- Behboudi A, Enlund F, Winnes M, Andren Y, Nordkvist A, Leivo I, Flaberg E, Szekely L, Makitie A, Grenman R, Mark J, Stenman G. Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene. Genes Chromosomes Cancer. 2006 May;45(5):470-81. PMID: #16444749#

- Behboudi A, Winnes M, Gorunova L, van den Oord JJ, Mertens F, Enlund F, Stenman G. Clear cell hidradenoma of the skin-a third tumor type with a t(11;19)—associated TORC1-MAML2 gene fusion. Genes Chromosomes Cancer. 2005 Jun;43(2):202-5. PMID: #15729701#

- Enlund F, Behboudi A, Andren Y, Oberg C, Lendahl U, Mark J, Stenman G. Altered Notch signaling resulting from expression of a WAMTP1-MAML2 gene fusion in mucoepidermoid carcinomas and benign Warthin’s tumors. Exp Cell Res. 2004 Jan 1;292(1):21-8. PMID: #14720503#