Mutations of RAS genes in endometrial polyps
| Autor: | Masataka Adachi, Kouji Banno, Daisuke Aoki, Yusuke Kobayashi, Eiichiro Tominaga, Kenjiro Kosaki, Megumi Yanokura, Takashi Takeda |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Cancer Research Gene mutation Biology medicine.disease_cause RAS mutation GTP Phosphohydrolases Proto-Oncogene Proteins p21(ras) endometrial polyp Polyps otorhinolaryngologic diseases medicine Endometrial Polyp Humans Exome neoplasms benign tumors Microdissection Uterine Diseases Mutation Endometrial cancer Membrane Proteins Articles General Medicine medicine.disease digestive system diseases atypical polypoid adenomyoma tumorigenesis surgical procedures operative Oncology endometrial cancer Cancer research Female KRAS Atypical polypoid adenomyoma Carcinogenesis |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2019.7353 |
| Popis: | Endometrial polyps are common, yet the molecular mechanisms underlying their formation and progression remain unclear. We examined gene mutations possibly related to the pathogenesis of endometrial polyps, as well as to their clinical features. Four premenopausal patients with endometrial polyps, who were not under drug treatment, were recruited. Whole exomes of endometrial polyps and peripheral blood lymphocytes were analyzed by next‑generation sequencing, and somatic mutations were derived by subtraction. Then, 35 samples of endometrial polyps and 12 samples of atypical polypoid adenomyoma were newly recruited to validate the identified mutations by polymerase chain reaction‑reverse sequence specific oligonucleotide method. The mutations were also analyzed in separate stromal and glandular components of the polyps after laser‑capture microdissection. Whole exome sequencing revealed that KRAS mutations were the only type of mutation detectable in multiple cases (2/4). Targeted mutation analysis revealed that 16 of 35 samples (45.7%) of endometrial polyps harbored RAS mutations. Mutation‑positive cases exhibited a significantly higher number of endometrial polyps (3.25±2.70 vs. 1.74±0.87, P=0.045). Laser‑capture microdissection in NRAS‑mutated endometrial polyps revealed that both stromal and glandular components harbored RAS mutations. There was no RAS mutation in 12 samples of atypical polypoid adenomyoma. This is the first report demonstrating that pathogenic RAS mutations are frequent in non‑treated endometrial polyps. RAS mutations may have an important role in tumorigenesis and in the formation of multiple endometrial polyps. |
| Databáze: | OpenAIRE |
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