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Somatic SF3B1 hotspot mutation in prolactinomas

The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tiss...

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Autores principales: Li, Chuzhong, Xie, Weiyan, Rosenblum, Jared S., Zhou, Jianyu, Guo, Jing, Miao, Yazhou, Shen, Yutao, Wang, Hongyun, Gong, Lei, Li, Mingxuan, Zhao, Sida, Cheng, Sen, Zhu, Haibo, Jiang, Tao, Ling, Shiying, Wang, Fei, Zhang, Hongwei, Zhang, Mingshan, Qu, Yanming, Zhang, Qi, Li, Guilin, Wang, Junmei, Ma, Jun, Zhuang, Zhengping, Zhang, Yazhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237453/
https://www.ncbi.nlm.nih.gov/pubmed/32427851
http://dx.doi.org/10.1038/s41467-020-16052-8
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author Li, Chuzhong
Xie, Weiyan
Rosenblum, Jared S.
Zhou, Jianyu
Guo, Jing
Miao, Yazhou
Shen, Yutao
Wang, Hongyun
Gong, Lei
Li, Mingxuan
Zhao, Sida
Cheng, Sen
Zhu, Haibo
Jiang, Tao
Ling, Shiying
Wang, Fei
Zhang, Hongwei
Zhang, Mingshan
Qu, Yanming
Zhang, Qi
Li, Guilin
Wang, Junmei
Ma, Jun
Zhuang, Zhengping
Zhang, Yazhuo
author_facet Li, Chuzhong
Xie, Weiyan
Rosenblum, Jared S.
Zhou, Jianyu
Guo, Jing
Miao, Yazhou
Shen, Yutao
Wang, Hongyun
Gong, Lei
Li, Mingxuan
Zhao, Sida
Cheng, Sen
Zhu, Haibo
Jiang, Tao
Ling, Shiying
Wang, Fei
Zhang, Hongwei
Zhang, Mingshan
Qu, Yanming
Zhang, Qi
Li, Guilin
Wang, Junmei
Ma, Jun
Zhuang, Zhengping
Zhang, Yazhuo
author_sort Li, Chuzhong
collection PubMed
description The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1(R625H)) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1(R625H) mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics.
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spelling pubmed-72374532020-05-27 Somatic SF3B1 hotspot mutation in prolactinomas Li, Chuzhong Xie, Weiyan Rosenblum, Jared S. Zhou, Jianyu Guo, Jing Miao, Yazhou Shen, Yutao Wang, Hongyun Gong, Lei Li, Mingxuan Zhao, Sida Cheng, Sen Zhu, Haibo Jiang, Tao Ling, Shiying Wang, Fei Zhang, Hongwei Zhang, Mingshan Qu, Yanming Zhang, Qi Li, Guilin Wang, Junmei Ma, Jun Zhuang, Zhengping Zhang, Yazhuo Nat Commun Article The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1(R625H)) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1(R625H) mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics. Nature Publishing Group UK 2020-05-19 /pmc/articles/PMC7237453/ /pubmed/32427851 http://dx.doi.org/10.1038/s41467-020-16052-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, Chuzhong
Xie, Weiyan
Rosenblum, Jared S.
Zhou, Jianyu
Guo, Jing
Miao, Yazhou
Shen, Yutao
Wang, Hongyun
Gong, Lei
Li, Mingxuan
Zhao, Sida
Cheng, Sen
Zhu, Haibo
Jiang, Tao
Ling, Shiying
Wang, Fei
Zhang, Hongwei
Zhang, Mingshan
Qu, Yanming
Zhang, Qi
Li, Guilin
Wang, Junmei
Ma, Jun
Zhuang, Zhengping
Zhang, Yazhuo
Somatic SF3B1 hotspot mutation in prolactinomas
title Somatic SF3B1 hotspot mutation in prolactinomas
title_full Somatic SF3B1 hotspot mutation in prolactinomas
title_fullStr Somatic SF3B1 hotspot mutation in prolactinomas
title_full_unstemmed Somatic SF3B1 hotspot mutation in prolactinomas
title_short Somatic SF3B1 hotspot mutation in prolactinomas
title_sort somatic sf3b1 hotspot mutation in prolactinomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237453/
https://www.ncbi.nlm.nih.gov/pubmed/32427851
http://dx.doi.org/10.1038/s41467-020-16052-8
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