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Characterization of Loss-of-Imprinting in Breast Cancer at the Cellular Level by Integrating Single-Cell Full-Length Transcriptome with Bulk RNA-Seq Data

Authors :
Muhammad Talal Amin
Louis Coussement
Tim De Meyer
Source :
Biomolecules, Vol 14, Iss 12, p 1598 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

Genomic imprinting, the parent-of-origin-specific gene expression, plays a pivotal role in growth regulation and is often dysregulated in cancer. However, screening for imprinting is complicated by its cell-type specificity, which bulk RNA-seq cannot capture. On the other hand, large-scale single-cell RNA-seq (scRNA-seq) often lacks transcript-level detail and is cost-prohibitive. Here, we address this gap by integrating bulk RNA-seq with full-length transcript scRNA-seq to investigate imprinting dynamics in breast cancer. By analyzing scRNA-seq data from 486 cancer cells across subtypes, we identified multiple SNPs in imprinted genes, including HM13, MEST (PEG1), SNHG14 and PEG10, showing consistent biallelic expression. Bulk RNA-seq, however, revealed that this biallelic expression arises from transcript-specific imprinting, rather than loss-of-imprinting (LOI). The imprinted SNPs identified in bulk RNA-seq predominantly demonstrate proper monoallelic expression in scRNA-seq. As a clear exception, an HER2+ breast cancer sample exhibited distinct LOI of MEST. Previous bulk RNA-seq-based observations about MEST LOI in breast cancer could not exclude a non-cancer cell impact, but our results validate that MEST LOI is cancer-specific. This study demonstrates the complementary utility of bulk and scRNA-seq in imprinting studies, confirming MEST LOI as a genuine event in breast cancer.

Details

Language :
English
ISSN :
2218273X
Volume :
14
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.f70d5b5ca3db43fd98606b5d684a4eda
Document Type :
article
Full Text :
https://doi.org/10.3390/biom14121598