The Role of Non-Coding RNAs in Chromosomal Instability in Cancer.

Chromosomal instability (CIN) is characterized by an increased frequency of changes in chromosome structure or number and is regarded as a hallmark of cancer. CIN plays a prevalent role in tumorigenesis and cancer progression by assisting the cancer cells' phenotypic adaptation to stress, which have been tightly linked to therapy resistance and metastasis. Both CIN-inducing and CIN-repressing agents are being clinically tested for the treatment of cancer to increase CIN levels to unsustainable levels leading to cell death or to decrease CIN levels to limit the development of drug resistance, respectively. Non-coding RNAs (ncRNAs) including microRNAs and long ncRNAs (lncRNAs) have been fundamentally implicated in CIN. The miR-22, miR-26a, miR-28, and miR-186 target important checkpoint proteins involved in mediating chromosomal stability and their expression modulation has been directly related to CIN occurrence. lncRNAs derived from telomeric, centrosomal, and enhancer regions play an important role in mediating genome stability, while specific lncRNA transcripts including genomic instability inducing RNA called Ginir, P53-responsive lncRNA termed as GUARDIN, colon cancer-associated transcript 2, PCAT2, and ncRNA activated by DNA damage called NORAD have been shown to act within CIN-associated pathways. In this review, we discuss how these ncRNAs either maintain or disrupt the stability of chromosomes and how these mechanisms could be exploited for novel therapeutic approaches targeting CIN in cancer patients. SIGNIFICANCE STATEMENT: Chromosomal instability increases tumor heterogeneity and thereby assists the phenotypic adaptation of cancer cells, causing therapy resistance and metastasis. Several microRNAs and long non-coding RNAs that have been causally linked to chromosomal instability could represent novel therapeutic targets. Understanding the role of non-coding RNAs in regulating different genes involved in driving chromosomal instability will give insights into how non-coding RNAs can be utilized toward modifying chemotherapeutic regimens in different cancers.

Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.