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The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers.
- Source :
- Nature Communications; 6/1/2022, Vol. 13 Issue 1, p1-13, 13p
- Publication Year :
- 2022
-
Abstract
- Molecular variation between geographical populations and subtypes indicate potential genomic heterogeneity and novel genomic features within CCA. Here, we analyze exome-sequencing data of 87 perihilar cholangiocarcinoma (pCCA) and 261 intrahepatic cholangiocarcinoma (iCCA) cases from 3 Asian centers (including 43 pCCAs and 24 iCCAs from our center). iCCA tumours demonstrate a higher tumor mutation burden and copy number alteration burden (CNAB) than pCCA tumours, and high CNAB indicates a poorer pCCA prognosis. We identify 12 significantly mutated genes and 5 focal CNA regions, and demonstrate common mutations in post-transcriptional modification-related potential driver genes METTL14 and RBM10 in pCCA tumours. Finally we demonstrate the tumour-suppressive role of METTL14, a major RNA N6-adenosine methyltransferase (m6A), and illustrate that its loss-of-function mutation R298H may act through m6A modification on potential driver gene MACF1. Our results may be valuable for better understanding of how post-transcriptional modification can affect CCA development, and highlight both similarities and differences between pCCA and iCCA. Cholangiocarcinoma is a heterogenous group of cancers, with large genetic variation seen within subtypes. Here, the authors find 12 significantly mutated genes and 5 focal CNA regions were found in perihilar cholangiocarcinoma, and identified METTL14 to have a potential tumour suppressive role. [ABSTRACT FROM AUTHOR]
- Subjects :
- CHOLANGIOCARCINOMA
GENETIC variation
METHYLTRANSFERASES
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 13
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 157212595
- Full Text :
- https://doi.org/10.1038/s41467-022-30708-7