De novo mutation of cancer-related genes associates with particular neurodevelopmental disorders
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ORIGINAL ARTICLE
De novo mutation of cancer-related genes associates with particular neurodevelopmental disorders Bin Li 1,2 & Kuokuo Li 3 & Di Tian 3 & Qiao Zhou 1,2 & Yali Xie 1,2 & Zhenghuan Fang 3 & Xiaomeng Wang 3 & Tengfei Luo 3 & Zheng Wang 1 & Yi Zhang 1 & Yijing Wang 3 & Qian Chen 1 & Qingtuan Meng 4 & Guihu Zhao 1,2 & Jinchen Li 1,2,3 Received: 20 January 2020 / Revised: 1 October 2020 / Accepted: 7 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Epidemiological studies have shown an increased prevalence of cancer in some patients with neurodevelopmental disorder (NDD); however, the genetic mechanisms regarding how cancer-related genes (CRGs) contribute to NDD remain unclear. We performed bioinformatic analyses on 219 CRGs from OMIM and de novo mutations (DNMs) from 16,498 patients with different NDDs and 3391 controls. Our results showed that autism spectrum disorder, undiagnosed neurodevelopmental disorder, congenital heart disease and intellectual disability, but not epileptic encephalopathy and schizophrenia, harboured significantly more putative functional DNMs in CRGs, compared with controls, providing genetic evidence supporting previous epidemiological surveys. We further detected 26 CRGs with recurrent putative functional DNMs that showed high expression in the human brain during the prenatal stage and in non-brain organs in adults. The proteins coded by the 26 CRGs and known NDD candidate genes formed a functional network that is involved in brain development and tumorigenesis. Overall, we proposed 39 cancer-targeting drugs that could be investigated for treating patients with NDD, which would be potentially cost-effective. In conclusion, DNMs contribute to specific NDDs and there may be a shared genetic basis between NDDs and cancer, highlighting the importance of considering cancer-targeting drugs with potential curative effects in patients with NDDs. Key messages • The contribution of DNMs in NDD is consistent with epidemiological surveys. • We highlighted 26 CRGs, including nine genes with more than five functional DNMs. • Specific expression patterns underlie the genetic mechanism of CRGs in NDD. • Specific functional networks underlie the genetic mechanism of CRGs in NDD. • The shared genetic aetiology suggests potential mutual treatment strategies. Keywords Cancer-related gene . Developmental disorder . De novo mutation . Expression pattern . Functional network
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00109-020-01991-y) contains supplementary material, which is available to authorized users. * Guihu Zhao [email protected]
2
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
* Jinchen Li [email protected]
3
Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410008, Hunan, China
1
4
Guangxi Clinical Research Center for Neurological Diseases, Affiliated Hospit
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