Luis Javier Galindo1, Tamara Hernández-Beeftink1, Ana Salas1, Yaiza Jung1, Ricardo Reyes1, Francisco Montes de Oca2, Mariano Hernández3, Teresa A Almeida4. 1. Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Universidad de la Laguna, Avda. Astrofísico Fco. Sánchez s/n, 38207 La Laguna, Tenerife, Spain. 2. Hospital Quironsalud, Poeta Rodríguez Herrera 1, Santa Cruz de Tenerife 38006, Tenerife, Spain. 3. Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Universidad de la Laguna, Avda. Astrofísico Fco. Sánchez s/n, 38207 La Laguna, Tenerife, Spain; Instituto de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de la Laguna, Avda. Astrofísico Fco. Sánchez s/n, 38207 La Laguna, Tenerife, Spain. 4. Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Universidad de la Laguna, Avda. Astrofísico Fco. Sánchez s/n, 38207 La Laguna, Tenerife, Spain; Instituto de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de la Laguna, Avda. Astrofísico Fco. Sánchez s/n, 38207 La Laguna, Tenerife, Spain. Electronic address: tacosalm@ull.edu.es.
Abstract
OBJECTIVE: Around 70% of uterine leiomyomas show MED12 mutations while overexpression of HMGA2 mRNA is also highly frequent in fibroids. However, previous studies suggested that alterations in both genes are mutually exclusive. In the present study, we searched for mutation in MED12 and analyzed the expression of HMGA2 in 20 uterine leiomyomas and their matched myometrium. METHODS: Normal and tumor tissue obtained from premenopausal women who underwent hysterectomy were collected after surgery and DNA, RNA and proteins were isolated and analyzed for MED12 mutations using Sanger sequencing, HMGA2 mRNA expression by quantitative PCR and HMGA2 protein detection by western blot and immunohistochemistry. RESULTS: 75% of the tumors displayed MED12 mutation while 65% of them showed overexpression of HMGA2 mRNA in leiomyomata compared to myometrial tissues (p = 0,0008). Interestingly, 50% of the tumors showed mutations in MED12 and overexpression of HMGA2 mRNA simultaneously, suggesting that alterations in both genes are relatively frequent in uterine leiomyomas. CONCLUSIONS: Contrary to the present findings, former studies showed that mutations in MED12 and overexpression of HMGA2 are mutually exclusive. Here, we observed that overexpression of HMGA2 mRNA in tumors measured by quantitative PCR and compared to myometrium is a common phenomenon in fibroids and is frequently associated with MED12 mutations. In addition, the common clonal origin of tumors overexpressing HMGA2 mRNA and its expression in few myometrial tissue points to HMGA2 up-regulation as an early event in leiomyoma tumorigenesis.
OBJECTIVE: Around 70% of uterine leiomyomas show MED12 mutations while overexpression of HMGA2 mRNA is also highly frequent in fibroids. However, previous studies suggested that alterations in both genes are mutually exclusive. In the present study, we searched for mutation in MED12 and analyzed the expression of HMGA2 in 20 uterine leiomyomas and their matched myometrium. METHODS: Normal and tumor tissue obtained from premenopausal women who underwent hysterectomy were collected after surgery and DNA, RNA and proteins were isolated and analyzed for MED12 mutations using Sanger sequencing, HMGA2 mRNA expression by quantitative PCR and HMGA2 protein detection by western blot and immunohistochemistry. RESULTS: 75% of the tumors displayed MED12 mutation while 65% of them showed overexpression of HMGA2 mRNA in leiomyomata compared to myometrial tissues (p = 0,0008). Interestingly, 50% of the tumors showed mutations in MED12 and overexpression of HMGA2 mRNA simultaneously, suggesting that alterations in both genes are relatively frequent in uterine leiomyomas. CONCLUSIONS: Contrary to the present findings, former studies showed that mutations in MED12 and overexpression of HMGA2 are mutually exclusive. Here, we observed that overexpression of HMGA2 mRNA in tumors measured by quantitative PCR and compared to myometrium is a common phenomenon in fibroids and is frequently associated with MED12 mutations. In addition, the common clonal origin of tumors overexpressing HMGA2 mRNA and its expression in few myometrial tissue points to HMGA2 up-regulation as an early event in leiomyoma tumorigenesis.
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