Tags

Type your tag names separated by a space and hit enter

MED12 alterations in both human benign and malignant uterine soft tissue tumors.
PLoS One. 2012; 7(6):e40015.Plos

Abstract

The relationship between benign uterine leiomyomas and their malignant counterparts, i.e. leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), is still poorly understood. The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas. In this study we asked whether such mutations could also be involved in leiomyosarcomas and STUMP oncogenesis. For this purpose we examined 33 uterine mesenchymal tumors by sequencing the hot-spot mutation region of MED12. We determined that MED12 is altered in 66.6% of typical leiomyomas as previously reported but also in 11% of STUMP and 20% of leiomyosarcomas. The mutated allele is predominantly expressed in leiomyomas and STUMP. Interestingly all classical leiomyomas exhibit MED12 protein expression while 40% of atypical leiomyomas, 50% of STUMP and 80% of leiomyosarcomas (among them the two mutated ones) do not express MED12. All these tumors without protein expression exhibit complex genomic profiles. No mutations and no expression loss were identified in an additional series of 38 non-uterine leiomyosarcomas. MED12 mutations are not exclusive to leiomyomas but seem to be specific to uterine malignancies. A previous study has suggested that MED12 mutations in leiomyomas could lead to Wnt/β-catenin pathway activation however our immunohistochemistry results show that there is no association between MED12 status and β-catenin nuclear/cytoplasmic localization. Collectively, our results show that subgroups of benign and malignant tumors share a common genetics. We propose here that MED12 alterations could be implicated in the development of smooth muscle tumor and that its expression could be inhibited in malignant tumors.

Authors+Show Affiliations

INSERM U916, Institut Bergonié Cancer Institute, Bordeaux, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22768200

Citation

Pérot, Gaëlle, et al. "MED12 Alterations in Both Human Benign and Malignant Uterine Soft Tissue Tumors." PloS One, vol. 7, no. 6, 2012, pp. e40015.
Pérot G, Croce S, Ribeiro A, et al. MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS ONE. 2012;7(6):e40015.
Pérot, G., Croce, S., Ribeiro, A., Lagarde, P., Velasco, V., Neuville, A., Coindre, J. M., Stoeckle, E., Floquet, A., MacGrogan, G., & Chibon, F. (2012). MED12 alterations in both human benign and malignant uterine soft tissue tumors. PloS One, 7(6), e40015. https://doi.org/10.1371/journal.pone.0040015
Pérot G, et al. MED12 Alterations in Both Human Benign and Malignant Uterine Soft Tissue Tumors. PLoS ONE. 2012;7(6):e40015. PubMed PMID: 22768200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MED12 alterations in both human benign and malignant uterine soft tissue tumors. AU - Pérot,Gaëlle, AU - Croce,Sabrina, AU - Ribeiro,Agnès, AU - Lagarde,Pauline, AU - Velasco,Valérie, AU - Neuville,Agnès, AU - Coindre,Jean-Michel, AU - Stoeckle,Eberhard, AU - Floquet,Anne, AU - MacGrogan,Gaëtan, AU - Chibon,Frédéric, Y1 - 2012/06/29/ PY - 2012/02/17/received PY - 2012/05/30/accepted PY - 2012/7/7/entrez PY - 2012/7/7/pubmed PY - 2012/12/10/medline SP - e40015 EP - e40015 JF - PloS one JO - PLoS ONE VL - 7 IS - 6 N2 - The relationship between benign uterine leiomyomas and their malignant counterparts, i.e. leiomyosarcomas and smooth muscle tumors of uncertain malignant potential (STUMP), is still poorly understood. The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas. In this study we asked whether such mutations could also be involved in leiomyosarcomas and STUMP oncogenesis. For this purpose we examined 33 uterine mesenchymal tumors by sequencing the hot-spot mutation region of MED12. We determined that MED12 is altered in 66.6% of typical leiomyomas as previously reported but also in 11% of STUMP and 20% of leiomyosarcomas. The mutated allele is predominantly expressed in leiomyomas and STUMP. Interestingly all classical leiomyomas exhibit MED12 protein expression while 40% of atypical leiomyomas, 50% of STUMP and 80% of leiomyosarcomas (among them the two mutated ones) do not express MED12. All these tumors without protein expression exhibit complex genomic profiles. No mutations and no expression loss were identified in an additional series of 38 non-uterine leiomyosarcomas. MED12 mutations are not exclusive to leiomyomas but seem to be specific to uterine malignancies. A previous study has suggested that MED12 mutations in leiomyomas could lead to Wnt/β-catenin pathway activation however our immunohistochemistry results show that there is no association between MED12 status and β-catenin nuclear/cytoplasmic localization. Collectively, our results show that subgroups of benign and malignant tumors share a common genetics. We propose here that MED12 alterations could be implicated in the development of smooth muscle tumor and that its expression could be inhibited in malignant tumors. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22768200/MED12_alterations_in_both_human_benign_and_malignant_uterine_soft_tissue_tumors_ L2 - http://dx.plos.org/10.1371/journal.pone.0040015 DB - PRIME DP - Unbound Medicine ER -