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FANC1 affects R-loop distribution resulting in tumor progression in LUAD

ABSTRACT: To plot the R-loop landscape of LUAD cells, we conducted DRIP-seq using S9.6, an anti-DNA/RNA hybrid antibody.We next tested the effect of FANCI deficiency on R-loop distribution and found that FANCI knockout clearly altered the R-loop landscape, showing a strong loss trend.Our analysis revealed that changes in R-loop distribution mediated by FANCI deficiency blocks the activity of the Ras signaling pathway, thereby suppressing tumor-cell proliferation and dissemination. Importantly, our study highlights the causal role of FANCI-mediated changes in R-loop distribution that leads to LUAD development

ORGANISM(S): Homo sapiens

PROVIDER: GSE248308 | GEO | 2023/11/23

REPOSITORIES: GEO

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Project description:<a href="https://cptac-data-portal.georgetown.edu/study-summary/S056" target="_blank">Proteogenomics of Lung Adenocarcinoma, Gillette et al., 2020 publication is here</a> Lung cancer is a leading cause of cancer death in the United States and in 2019 it is estimated that there will be over 228,000 new cases (<a href="https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html" target="_blank">American Cancer Society</a>). There are two main types, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). A majority of patients (85%) have NSCLC, with a significant portion of those individuals having a histological subtype lung adenocarcinoma (LUAD) <a href="https://www.ncbi.nlm.nih.gov/pubmed/29364287" target="_blank">Herbst et al., 2018 Nature</a>. To advance the proteogenomic understanding of LUAD, the CPTAC program has investigated 111 tumors, (with 102 tumors paired with normal adjacent tissue samples) and subjected these samples to global proteome and phosphoproteome analysis. An optimized workflow for mass spectrometry of tissues using isobaric tags (TMT (tandem mass tags)-10) was used (<a href="https://www.ncbi.nlm.nih.gov/pubmed/29988108" target="_blank">Mertins et al., Nature Protocols 2018</a>). Proteome and phosphoproteome data from the LUAD discovery cohort is available below along with peptide spectrum matches (PSMs) and protein summary reports from the CPTAC common data analysis pipeline (CDAP).Clinical Data for LUAD tumors are provided below. Updates will be available as the LUAD cohort characterization proceeds. Genomic Data for LUAD tumors is available from the NCI Genomic Data Commons (GDC), <a href="https://portal.gdc.cancer.gov/projects/CPTAC-3" target="_blank">here</a> Imaging Data for LUAD tumors is available from NCI, The Cancer Imaging Archive (TCIA), <a href="https://wiki.cancerimagingarchive.net/display/Public/CPTAC-LUAD" target="_blank">here</a> This release includes over 4500 files and 914 GB of data. <ul><li>Dataset imported into MassIVE from <a href="https://cptac-data-portal.georgetown.edu/study-summary/S046">https://cptac-data-portal.georgetown.edu/study-summary/S046</a> on 01/29/21</li></ul>

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FANC1 affects R-loop distribution resulting in tumor progression in LUAD

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