Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome

Abstract

Epidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias the numbers. As to NDD-associated mutations, in most cases, they are germline while cancer mutations are sporadic, emerging during life. However, somatic mosaicism can spur NDDs, and cancer-related mutations can be germline. NDDs and cancer share proteins, pathways, and mutations. Here we ask (i) exactly which features they share, and (ii) how, despite their commonalities, they differ in clinical outcomes. To tackle these questions, we employed a statistical framework followed by network analysis. Our thorough exploration of the mutations, reconstructed disease-specific networks, pathways, and transcriptome levels and profiles of autism spectrum disorder (ASD) and cancers, point to signaling strength as the key factor: strong signaling promotes cell proliferation in cancer, and weaker (moderate) signaling impacts differentiation in ASD. Thus, we suggest that signaling strength, not activating mutations, can decide clinical outcome.

The allosteric mechanism of mTOR activation can inform bitopic inhibitor optimization

“…These allele origins of mTOR variants can share identical mutations, suggesting that individuals with disorder diseases may have an elevated risk of developing cancer. 93,94…”

Association between Autism Spectrum Disorder and Cancer - a Review from the Literature

“…(Vuattoux et al, 2021). In one study exploration of the mutations, reconstructed disorder specific networks, pathways, and transcriptome levels and profiles of autism spectrum disorder (ASD) and cancers, point to signalling strength as the key factor: strong signalling promotes cell proliferation in cancer, and weaker (moderate) signalling impacts differentiation in ASD (Yavuz et al, 2023). In this article the role of epigenetics and the post-translation modifications in both disorders is not analysed and that could be a topic for another article.…”

Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide

“…Cancer onset is associated with abnormal cell proliferation ( Brunner and Finley, 2023 ; de Visser and Joyce, 2023 ), while NDDs are mostly related to dysregulated differentiation ( Khodosevich and Sellgren, 2023 ). In terms of cell cycle signaling ( Demeter et al, 2022 ), they differ in signaling strength and duration ( Yavuz et al, 2023a ). Under physiologic conditions, mitogen-promoted strong signaling bursts over short duration are associated with cell proliferation.…”