Fusion gene recurrence in non-small cell lung cancers and its association with cigarette smoke exposure.

Background: Lung cancer remains the leading cause of cancer-related deaths in the US despite novel treatment protocols, with about 235,000 new cases and 131,000 deaths expected from this cancer in 2021 alone. Lung adenocarcinoma and squamous cell carcinoma, which are both subtypes of non-small cell lung cancer, account for most lung cancer cases, and comparing the molecular signatures in these two cancers can identify novel mechanisms that contribute to non-small cell lung cancer oncogenesis.

Methods: We, in this study, performed a comprehensive gene fusion profiling of these cancers, which is understudied in lung cancers.

Pan-Cancer Analysis Reveals the Diverse Landscape of Novel Sense and Antisense Fusion Transcripts.

Gene fusions that contribute to oncogenicity can be explored for identifying cancer biomarkers and potential drug targets. To investigate the nature and distribution of fusion transcripts in cancer, we examined the transcriptome data of about 9,000 primary tumors from 33 different cancers in TCGA (The Cancer Genome Atlas) along with cell line data from CCLE (Cancer Cell Line Encyclopedia) using ChimeRScope, a novel fusion detection algorithm. We identified several fusions with sense (canonical, 39%) or antisense (non-canonical, 61%) transcripts recurrent across cancers.

Identification of Fusion Transcripts from Unaligned RNA-Seq Reads Using ChimeRScope.

Fusion transcripts that are frequent in cancer can be exploited to understand the mechanisms of malignancy and can serve as diagnostic or prognostic markers. Several algorithms have been developed to predict fusion transcripts from DNA or RNA data. The majority of these algorithms align sequencing reads to the reference transcriptome for predicting fusions; however, this results in several undetected fusions due to the highly perturbed nature of cancer genomes.

Downregulation of an Evolutionary Young miR-1290 in an iPSC-Derived Neural Stem Cell Model of Autism Spectrum Disorder.

The identification of several evolutionary young miRNAs, which arose in primates, raised several possibilities for the role of such miRNAs in human-specific disease processes. We previously have identified an evolutionary young miRNA, miR-1290, to be essential in neural stem cell proliferation and neuronal differentiation. Here, we show that miR-1290 is significantly downregulated during neuronal differentiation in reprogrammed induced pluripotent stem cell- (iPSC-) derived neurons obtained from idiopathic autism spectrum disorder (ASD) patients.