Possible involvement of genome-wide near-haploidy and MEN1 mutation in the molecular pathogenesis of pituitary carcinoma: analysis by whole exome sequencing
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ID: 315596
2026
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Abstract
Abstract Background Pituitary carcinoma is a rare tumor, accounting for 0.12% of pituitary neuroendocrine tumors (PitNETs), that is derived from adenohypophyseal cells with craniospinal or systemic metastasis. While most PitNETs have a benign course, pituitary carcinoma has a poor prognosis, and its underlying molecular mechanism remains unclear. Here, we explored the molecular pathogenesis of pituitary carcinoma using whole exome sequencing (WXS). Methods Tumor tissue samples were collected from patients diagnosed with pituitary carcinoma from April 2000 to March 2024 through multi-institutional joint research. DNA extraction and WXS were performed on the collected samples, and we analyzed the obtained data. Results Five samples from four patients were collected (four men, mean age 57.5 years). DNA extraction and WXS were performed on the five samples. Gene mutation analysis revealed MEN1 mutations in three samples. Copy number analysis showed unstable chromosomal conditions of genome-wide hypoploidy, which can be called near-haploidy, in three samples. Conclusions This study showed that pituitary carcinoma had genome-wide hypoploidy, that is, genome-wide chromosomal instability and MEN1 mutations as a possible recurrent mutation. Accumulated or original chromosomal instability may lead to the development of pituitary carcinoma from PitNET, and MEN1 mutations may also play an important role in the pathogenesis of pituitary carcinoma. These findings may lead to strategies for earlier diagnosis and new treatments for this disease.
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| Authors | Satoru Kida, Takuma Nakashima, Satoshi Baba, Shinichiro Koizumi, Miho Yamashita, Sumihito Nobusawa, Chie Inomoto, Hiroyoshi Kino, Eiichi Ishikawa, Kazuhito Takeuchi, Tetsuya Nagatani, Ryuta Saito, Shingo Fujio, Ryosuke Hanaya, Joji Ishida, Shota Tanaka, Isao Date, Yasuyuki Kinoshita, A Taguchi, Yoshitaka Narita, Hiromichi Suzuki, Kazuhiko Kurozumi |
| Journal | Neuro-Oncology Advances |
| Year | 2026 |
| DOI |
10.1093/noajnl/vdag146
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| URL | |
| Keywords | Keywords not found |
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