Impact of CRTC1/3-MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma

Okumura, Yoshihide; Miyabe, Satoru; Nakayama, Tadanobu; Fujiyoshi, Yukio; Hattori, Hideo; Shimozato, Kazuo; Inagaki, Hiroshi

doi:10.1111/j.1365-2559.2011.03890.x

Cited by 71 publications

(68 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We previously reported that both CRTC1-MAML2-positive and CRTC3-MAML2-positive mucoepidermoid carcinomas are associated with mild histopathological features and a favorable clinical outcome compared with fusion-negative carcinomas. (7,12,13) Our present data show that the X-MAML2 carcinomas might also possess favorable tumor features similar to those positive for CRTC1/3-MAML2 fusions. However, it should be noted that there were minor differences between the three groups, such as differential expression of wild type MAML2 transcripts, lower patient age in the CRTC3-MAML2 fusion group and possibly poorer disease-free survival in CRTC1-MAML2 fusion groups.…”

Section: Discussionsupporting

confidence: 57%

“…A total of 95 cases were included in this study, some of which were also incorporated in our previous studies. (7,12,13) All tumor samples were fixed in formalin and embedded in paraffin. Informed consent was obtained, and the study was approved by the institutional review board of Nagoya City University and conducted in accordance with the Declaration of Helsinki.…”

mentioning

confidence: 99%

“…(13) CRTC1/3-MAML2 fusions have been detected using an RT-PCR technique, assuming that exon 1 of CRTC1/3 genes is fused to exons 2-5 of the MAML2 gene. (7,8,12,13) However, there would be unknown breakpoints in both CRTC1/3 and MAML2, and, therefore, the current RT-PCR systems might not be capable of covering unknown CRTC1/3-MAML2 fusion variants. In addition, RT-PCR may be unsuitable for detecting the gene fusions when the amount of the fusion transcripts is significantly low.…”

mentioning

confidence: 99%

“…These findings suggest that both CRTC1-MAML2 and CRTC3-MAML2 fusions may be associated with mucoepidermoid carcinoma cases with favorable clinicopathological tumor features. (13) CRTC1/3-MAML2 fusions have been detected using an RT-PCR technique, assuming that exon 1 of CRTC1/3 genes is fused to exons 2-5 of the MAML2 gene. (7,8,12,13) However, there would be unknown breakpoints in both CRTC1/3 and MAML2, and, therefore, the current RT-PCR systems might not be capable of covering unknown CRTC1/3-MAML2 fusion variants.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

et al. 2012

Self Cite

View full text Add to dashboard Cite

CRTC1-MAML2 and CRTC3-MAML2 fusions have been associated with favorable clinicopathological features of mucoepidermoid carcinomas. However, the significance of the MAML2 gene split has not been fully clarified. In the present study, 95 mucoepidermoid carcinomas (paraffin-embedded materials) were analyzed for CRTC1-MAML2 and CRTC3-MAML2 fusions by RT-PCR and for the MAML2 gene split by FISH. Quantitative RT-PCR for the CRTC1-MAML2 transcript was performed in selected cases. MLL gene involvement, which has been reported in some leukemia cases, was examined by FISH in fusion partner-unknown cases. CRTC1-MAML2 and CRTC3-MAML2 fusions were detected in 37 and 6 cases, respectively. The MAML2 gene split was detected in 62 cases, which included all CRTC1/3-MAML2 fusion-positive cases. The level of CRTC1-MAML2 transcript expression was highly variable, and its clinicopathological impact was unclear. The MLL gene split was not detected. Mucoepidermoid carcinomas negative for CRTC1/3-MAML2 and positive for the MAML2 gene split (n = 19) showed favorable clinicopathological tumor features similar to those positive for CRTC1/3-MAML2 fusions. Compared with negative cases (n = 33), mucoepidermoid carcinomas positive for the MAML2 split (n = 62) were associated with lower patient age, a mild female predilection, a smaller tumor size, less frequent nodal metastasis, a lower clinical stage, a lower histological grade, and longer overall and disease-free survival. The MAML2 gene split emerged as an independent prognostic factor for both overall and disease-free survival in multivariate prognostic analysis. The presence of the MAML2 gene split defines a distinct mucoepidermoid carcinoma subset that is associated clinicopathologically with favorable tumor features. (Cancer Sci 2013; 104: 85-92) M ucoepidermoid carcinomas represent 5% of all salivary gland tumors and 20% of salivary malignancies.(1,2) A subset of these carcinomas has been associated with a recurring chromosomal translocation, t(11;19)(q21;p13), which generates a fusion protein composed of the N-terminal of cAMP response element-binding protein (CREB)-regulated transcription coactivator 1 (CRTC1), also called MECT1, TORC1 or WAMP1, and the C-terminal of mastermind-like gene 2 (MAML2).(3-6) Recent data suggest that CRTC1-MAML2 induced-activation of CREB is critical for cell transformation.(5,6) CTCR1-MAML2 fusion has been detected in 40-80% of primary salivary gland mucoepidermoid carcinomas, and we and other research groups have shown that the fusion gene is associated with a distinct tumor subset with an indolent clinical course. and in Nakayama et al. (12) we reveal that CRTC3-MAML2 fusion-positive mucoepidermoid carcinoma cases have an excellent prognosis. These findings suggest that both CRTC1-MAML2 and CRTC3-MAML2 fusions may be associated with mucoepidermoid carcinoma cases with favorable clinicopathological tumor features. (13) CRTC1/3-MAML2 fusions have been detected using an RT-PCR technique, assuming that exon 1 of CRTC1/3 genes is fused to exons 2-5 of th...

show abstract

Section: Discussionsupporting

confidence: 57%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…19 When positive for the fusions CRTC1eMAML2 or CRTC3eMAML2, even 'high-risk' patients, including those with a higher histological grade or an advanced clinical stage, showed an excellent prognosis. 20 Thus, it has been proposed that fusionpositive MECs should be regarded as representing a distinctive entity separate from fusion-negative cases. 20 Recently, the EWSR1-POU5F1 fusion gene was documented in mucoepidermoid carcinomas of salivary gland as well as in hidradenoma of skin, providing further evidence for a genetic link between these two tumour types.…”

Section: Introductionmentioning

confidence: 99%

Molecular advances in salivary gland pathology and their practical application

Skálová

Vaněček

Simpson

et al. 2012

Diagnostic Histopathology

View full text Add to dashboard Cite

Global Burden, Classification, Pathobiology, Genetics and Prognosis of Salivary Gland Neoplasms

de Souza,

Lopes,

Vargas

et al. 2024

Pathological Basis of Oral and Maxillofacial Diseases

View full text Add to dashboard Cite

Impact of CRTC1/3-MAML2 fusions on histological classification and prognosis of mucoepidermoid carcinoma

Abstract: Molecular AFIP classification may be useful in predicting the prognosis of patients with MEC.

Cited by 71 publications

References 17 publications

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

Molecular advances in salivary gland pathology and their practical application

Global Burden, Classification, Pathobiology, Genetics and Prognosis of Salivary Gland Neoplasms

Contact Info

Product

Resources

About