Comprehensive screening for <i><scp>MED</scp>12</i> mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours

Yuan, Chang‐Tsu; Huang, Wen Ching; Lee, Cheng‐Han; Lin, Ming-Nan; Lee, Chen Hui; Kao, Yu-Chien; Huang, Hsuan Ying; Kuo, Kuan-Ting; Lee, Jen‐Chieh

doi:10.1111/his.13156

Cited by 7 publications

(6 citation statements)

References 33 publications

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“…Studies have shown that MED12 mutations in fibroadenomas are associated with dysregulation of estrogen signaling ( 27 ). This suggests that MED12 mutations may play a crucial oncogenic role in estrogen-related ESS ( 28 ). The study reveals that mutations in exon 2 of MED12 have been identified in ESS carrying the JAZF1-SUZ12 or JAZF1-PHF1 fusion genes.…”

Section: Discussionmentioning

confidence: 99%

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Intravenous metastasis of unexpected uterine sarcoma in the context of uterine fibroids: case report and literature review

Huang,

Zhang,

Wang

et al. 2024

Front. Oncol.

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ObjectiveEndometrial stromal tumors are rare and complex mesenchymal tumors that often present with clinical symptoms similar to uterine leiomyomas. Due to their atypical nature, they are prone to be misdiagnosed or overlooked by healthcare professionals. This study presents a case report of an incidentally discovered endometrial stromal sarcoma with venous metastasis, which was initially misdiagnosed as a uterine leiomyoma. In addition, this study reviews previously documented cases of similar tumors.Case reportDuring a routine medical examination in 2016, a 50-year-old woman was diagnosed with uterine fibroids. In June 2020, she began experiencing moderate, irregular vaginal bleeding. Nevertheless, a histopathological examination indicated an endometrial stromal sarcoma with a striking amalgamation of both low-grade and high-grade features. Molecular analysis identified a rare MED12 gene mutation. The patient underwent total hysterectomy, bilateral salpingectomy, and resection of the metastatic lesions. Postoperative management included radiotherapy, chemotherapy, and hormone therapy. After completion of chemotherapy, the patient was followed up for 27 months with no evidence of tumor recurrence.ConclusionThis case report highlights the importance of pathological, immunohistochemical, and molecular aspects of this rare tumor involving the inferior vena cava and showing the presence of atypical gene mutations. The successful treatment outcome further emphasizes the importance of advances in diagnostic modalities for managing rare tumors like this.

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Section: Discussionmentioning

confidence: 99%

“…The study reveals that mutations in exon 2 of MED12 have been identified in ESS carrying the JAZF1-SUZ12 or JAZF1-PHF1 fusion genes. These mutations may confer additional oncogenic advantages ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Intravenous metastasis of unexpected uterine sarcoma in the context of uterine fibroids: case report and literature review

Huang,

Zhang,

Wang

et al. 2024

Front. Oncol.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, the MED12 gene is closely related to uterine leiomyoma [ 17 ]. The 70% of uterine leiomyomas have point mutations in the MED12 gene, and all relevant point mutations are concentrated in exon 2 [ 17 ]. MED12 mutations alter the functioning of the MED12 protein, thus disrupting normal cell signalling and repair regulation of cell growth and other functions, resulting in uncontrolled cell growth and tumorigenesis [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing Analysis of 3 Uterine Adenosarcomas with Heterogeneously Differentiated Genomic Mutations

Li,

Meng,

Luo

et al. 2023

International Journal of Analytical Chemistry

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Uterine adenosarcoma (UA) is an uncommon mixed tumor containing a benign to at most mildly atypical epithelial component and a sarcoma-like stroma, usually a low-grade, stromal component, with rare heterogeneous elements. Currently, tumor etiology is largely unknown. To better understand the gene mutations in UA, next-generation sequencing (NGS) technology analysis was performed. This study showed that two low-grade UAs with heterologous components had ATRX gene frameshift mutation, and one patient had a MED12 missense mutation. Copy number amplification genes were mainly observed on chromosome 12q13–15. In this study, PIK3/AKT/PTEN pathway mutations were found to be common in adenosarcoma. In addition, a rare BCORL1-PRR14L fusion mutation was also identified. These findings provide a basis for future research into these molecular changes in tumorigenesis and targeted therapy.

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“…The molecular background of adenomyomas is not well known and most studies looking into their genetic and molecular features have focused on the rare subtype of atypical polypoid adenomyoma (APA) (Takahashi et al , 2014; Nemejcova et al , 2015; Yuan et al , 2017). Here, we have analysed the contribution of uterine leiomyoma driver events— MED12 mutations, HMGA2 overexpression, and FH inactivation—in 21 adenomyoma samples from 21 patients.…”

Section: Introductionmentioning

confidence: 99%

MED12 mutations and fumarate hydratase inactivation in uterine adenomyomas

Heikkinen

Äyräväinen

Hänninen

et al. 2018

Human Reproduction Open

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STUDY QUESTION Do the uterine leiomyoma driver events – mediator complex subunit 12 ( MED12 ) mutations, high mobility group AT-hook (HMGA2) overexpression, and fumarate hydratase (FH) inactivation – also contribute to the development of uterine adenomyomas? SUMMARY ANSWER MED12 mutations and FH deficiency occur in a subset of uterine adenomyomas, but at lower frequencies than in leiomyomas. WHAT IS KNOWN ALREADY Uterine adenomyomas are benign tumours with clinical features very similar to uterine leiomyomas. Mutations affecting MED12 , HMGA2 and FH account for up to 80–90% of leiomyomas, but their contribution to adenomyomas is not known. STUDY DESIGN, SIZE, DURATION Formalin-fixed paraffin-embedded adenomyoma samples from 21 patients operated on during 2012–2014 were collected at the pathology department’s archives and analysed for uterine leiomyoma driver events. PARTICIPANTS/MATERIALS, SETTING, METHODS Adenomyoma diagnoses were verified by a specialized pathologist and representative areas were marked on haematoxylin-eosin slides. DNA was extracted from the tissue samples and sequenced to detect mutations in MED12 . Expression levels of HMGA2 and 2SC, a robust indirect method to detect FH inactivation, were analysed by immunohistochemistry (IHC). The coding region of FH was sequenced in one adenomyoma sample showing strong 2SC staining as well as in the same patient’s normal tissue sample. All patients’ medical histories were collected and reviewed. MAIN RESULTS AND THE ROLE OF CHANCE MED12 mutation c.131G > A, p.G44D, the most common mutation in uterine leiomyomas, was identified in two samples (2/21; 9.5%). One adenomyoma displayed strong 2SC positivity and subsequent sequencing revealed a frameshift FH mutation c.911delC, p.P304fs in the tumour. The mutation was also present in the patient’s normal tissue sample, indicating that she has a hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. HMGA2 protein expression was normal in all adenomyomas. LIMITATIONS, REASONS FOR CAUTION Restricted sample size limits the determination of exact mutation frequencies of the studied aberrations in adenomyomas. WIDER IMPLICATIONS OF THE FINDINGS Uterine leiomyoma driver mutations do contribute to the development of some adenomyomas. We also report an adenomyoma in the context of hereditary HLRCC syndrome. Despite clinical similarities, the pathogenic mechanisms of adenomyomas and leiomyomas are likely different. Large-scale genomic analyses are warranted to elucidate the complete molecular background of adenomyomas. STUDY FUNDING/COMPETING INTERE...

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Comprehensive screening for MED12 mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours

Abstract: These MED12-mutated adenosarcoma-like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.

Cited by 7 publications

References 33 publications

Intravenous metastasis of unexpected uterine sarcoma in the context of uterine fibroids: case report and literature review

Intravenous metastasis of unexpected uterine sarcoma in the context of uterine fibroids: case report and literature review

Next-Generation Sequencing Analysis of 3 Uterine Adenosarcomas with Heterogeneously Differentiated Genomic Mutations

MED12 mutations and fumarate hydratase inactivation in uterine adenomyomas

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