クボクラ（イシカワ）　マユミ   Ishikawa-Kubokura Mayumi   窪倉（石川）　真由美    所属   東邦大学  医学部 医学科（大森病院）    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	An Excess of CYP24A1, Lack of CaSR, and a Novel lncRNA Near the PTH Gene Characterize an Ectopic PTH-Producing Tumor.
掲載誌名	正式名：Journal of the Endocrine Society
掲載区分	国外
巻・号・頁	1(6),pp.691-711
著者・共著者	Kosuke Uchida,Yuji Tanaka,Hitoshi Ichikawa,Masato Watanabe,Sachiyo Mitani,Koji Morita,Hiroko Fujii,Mayumi Ishikawa,Gen Yoshino,Hiroko Okinaga,Genta Nagae,Hiroyuki Aburatani,Yoshifumi Ikeda,Takao Susa,Mimi Tamamori-Adachi,Toshio Fukusato,Hiroshi Uozaki,Tomoki Okazaki,Masayoshi Iizuka
発行年月	2017/06/01
概要	Thus far, only 23 cases of the ectopic production of parathyroid hormone (PTH) have been reported. We have characterized the genome-wide transcription profile of an ectopic PTH-producing tumor originating from a retroperitoneal histiocytoma. We found that the calcium-sensing receptor (CaSR) was barely expressed in the tumor. Lack of CaSR, a crucial braking apparatus in the presence of both intraparathyroid and, probably, serendipitous PTH expression, might contribute strongly to the establishment and maintenance of the ectopic transcriptional activation of the PTH gene in nonparathyroid cells. Along with candidate drivers with a crucial frameshift mutation or copy number variation at specific chromosomal areas obtained from whole exome sequencing, we identified robust tumor-specific cytochrome P450 family 24 subfamily A member 1 (CYP24A1) overproduction, which was not observed in other non-PTH-expressing retroperitoneal histiocytoma and parathyroid adenoma samples. We then found a 2.5-kb noncoding RNA in the PTH 3'-downstream region that was exclusively present in the parathyroid adenoma and our tumor. Such a co-occurrence might act as another driver of ectopic PTH-producing tumorigenesis; both might release the control of PTH gene expression by shutting down the other branches of the safety system (e.g., CaSR and the vitamin D3-vitamin D receptor axis).
DOI	10.1210/js.2017-00063
PMID	29264523