How can same-gene mutations promote both cancer and developmental disorders?

Abstract

This review offers why same-gene mutations can lead to cancer and neurodevelopmental disorders and why a high risk of cancer.

Neurodevelopmental disorders, immunity, and cancer are connected

“…Cancer largely results from sporadic, somatic mutations emerging throughout life. Mutations are often in the same proteins, and often are common to cancer and neurodevelopmental disorders, leading to questions ( Nussinov et al., 2022a ) such as “how certain oncogenic mutations can promote cancer while others in the same proteins — or even the same mutations — can provoke other syndromes” and “ why patients, with neurodevelopmental disorders are more prone to cancer. ” These have recently been taken up and are addressed below.…”

“…Expression patterns of cells in-between these areas are delayed, likely linked to the identities of the gained interactions ( Curry and Glasgow, 2021 ; Luo et al., 2021 ; Rubenstein, 2011 ; Szczupak et al., 2021 ). As examples of locations and function, in early and mid-fetal development, ASD risk genes in prefrontal and primary motor cortices, striatum, cerebellum, and medial dorsal nucleus of the thalamus express at high levels ( Nussinov et al., 2022a ). Connective tissue dysplasia is common in patients with NF1 microdeletions and include CNS cancers in the brain or spinal cord, astrocyte cells that support nerve cells, peripheral nerve sheath tumors, and more ( Mensink et al., 2006 ).…”

“…Recently, we asked how same-gene mutations can promote both cancer and neurodevelopmental disorders and why patients with neurodevelopmental disorders are more prone to cancer ( Nussinov et al., 2022a ). We proposed that these questions can be understood in terms of four components: first, the expression level of the protein in the type-specific cell; second, the mutation strength; third, the timing of the protein (and mRNA) expression during embryonic development versus in the differentiated state; and fourth, the expression levels of proteins in the pathway through which the signal propagates.…”

“…Cancer is connected to immunity and inflammation. Neurodevelopmental disorders are connected to higher likelihood of cancer [e.g., ( Chiang et al., 2015 ; Crespi, 2011 ; Dangles et al., 2021 ; Gangfuss et al., 2022 ; Morton et al., 2021 ; Nussinov et al., 2022a ; Qi et al., 2016 ; Rauen, 2013 ; Zhang et al., 2021b ),]. They are also connected to immunity and inflammation [e.g., ( Bodnar et al., 2020 ; Boulanger-Bertolus et al., 2018 ; Cowan and Petri, 2018 ; Garay and McAllister, 2010 ; Jiang et al., 2018 ; Solek et al., 2018 ; Sotgiu et al., 2020 ; Tremblay, 2021 ; van Eeden et al., 2021 ),].…”

“…The literature abounds with publications describing explorations, data, and reviews on the connections of cancer, inflammation, and immunity. Over the last few years, the interest in the connection between cancer and neurodevelopmental disorders has also been soaring (overviewed in ( Nussinov et al., 2022a ), and references therein) and recently in the connection between neurodevelopmental disorders and immunity as well. Here, we look at these connections and the complex common and distinct nature of their relationships and scenarios.…”