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Background <p>Uterine adenomatoid tumors (UATs) are rare benign mesothelial neoplasms with poorly characterized molecular features. Comprehensive genomic profiling of UATs remains limited.</p> Methods <p>Targeted sequencing of 20 pathologically confirmed UATs was performed using a 641-gene panel. Immunohistochemical (IHC) analyses were conducted to assess protein expression patterns. Functional assays were performed in the Ishikawa endometrial carcinoma cell line to provide preliminary insight into the potential biological impact of <i>KMT5A</i> knockdown. Publicly available datasets (TCGA and cBioPortal) were analyzed to place these alterations into a broader molecular context across gynecologic malignancies.</p> Results <p>Recurrent mutations in <i>KMT5A</i> and <i>KMT2C</i> were identified in all cases (20/20, 100%), with consistent co-occurrence across the cohort. Additional alterations were observed in <i>HLA-B</i> (65%), <i>HLA-A</i> (50%), <i>ROS1</i> (45%), <i>TRAF7</i> (45%), <i>SDHA</i> (30%), and <i>KMT2A</i> (30%). IHC analysis demonstrated higher expression of <i>TRAF7</i>, <i>γ-H2AX</i>, <i>CALB2</i>, and <i>Ki-67</i> in tumors with elevated <i>KMT5A</i> expression. <i>KMT5A</i> knockdown in Ishikawa cells reduced proliferative and migratory capacity. Comparative analyses indicated that <i>KMT5A</i> mutations are uncommon in gynecologic malignancies (&lt; 3%), whereas <i>KMT2C</i> alterations are more broadly distributed.</p> Conclusions <p>UATs exhibit a distinctive mutational profile characterized by recurrent <i>KMT5A</i> and <i>KMT2C</i> co-mutations. These findings provide a comprehensive molecular characterization of UATs and suggest that recurrent alterations in chromatin-regulatory genes may represent characteristic genomic features that warrant further investigation.</p>

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Genomic characterization of uterine adenomatoid tumors reveals recurrent alterations in KMT5A and KMT2C

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月17日

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  • Shufeng Kang,
  • Fangfang Xu,
  • Juan Tao,
  • Guofang Chen,
  • Shuangdi Li

摘要

Background

Uterine adenomatoid tumors (UATs) are rare benign mesothelial neoplasms with poorly characterized molecular features. Comprehensive genomic profiling of UATs remains limited.

Methods

Targeted sequencing of 20 pathologically confirmed UATs was performed using a 641-gene panel. Immunohistochemical (IHC) analyses were conducted to assess protein expression patterns. Functional assays were performed in the Ishikawa endometrial carcinoma cell line to provide preliminary insight into the potential biological impact of KMT5A knockdown. Publicly available datasets (TCGA and cBioPortal) were analyzed to place these alterations into a broader molecular context across gynecologic malignancies.

Results

Recurrent mutations in KMT5A and KMT2C were identified in all cases (20/20, 100%), with consistent co-occurrence across the cohort. Additional alterations were observed in HLA-B (65%), HLA-A (50%), ROS1 (45%), TRAF7 (45%), SDHA (30%), and KMT2A (30%). IHC analysis demonstrated higher expression of TRAF7, γ-H2AX, CALB2, and Ki-67 in tumors with elevated KMT5A expression. KMT5A knockdown in Ishikawa cells reduced proliferative and migratory capacity. Comparative analyses indicated that KMT5A mutations are uncommon in gynecologic malignancies (< 3%), whereas KMT2C alterations are more broadly distributed.

Conclusions

UATs exhibit a distinctive mutational profile characterized by recurrent KMT5A and KMT2C co-mutations. These findings provide a comprehensive molecular characterization of UATs and suggest that recurrent alterations in chromatin-regulatory genes may represent characteristic genomic features that warrant further investigation.