Genetic alterations of SUGP1 mimic mutant-SF3B1 splice pattern in lung adenocarcinoma and other cancers.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
18
05
2020
accepted:
01
10
2020
revised:
30
09
2020
pubmed:
16
10
2020
medline:
17
4
2021
entrez:
15
10
2020
Statut:
ppublish
Résumé
Genes involved in 3'-splice site recognition during mRNA splicing constitute an emerging class of oncogenes. SF3B1 is the most frequently mutated splicing factor in cancer, and SF3B1 mutants corrupt branchpoint recognition leading to usage of cryptic 3'-splice sites and subsequent aberrant junctions. For a comprehensive determination of alterations leading to this splicing pattern, we performed a pan-TCGA screening for SF3B1-specific aberrant acceptor usage. While the most of aberrant 3'-splice patterns were explained by SF3B1 mutations, we also detected nine SF3B1 wild-type tumors (including five lung adenocarcinomas). Genomic profile analysis of these tumors identified somatic mutations combined with loss-of-heterozygosity in the splicing factor SUGP1 in five of these cases. Modeling of SUGP1 loss and mutations in cell lines showed that both alterations induced mutant-SF3B1-like aberrant splicing. Our study provides definitive evidence that genetic alterations of SUGP1 genocopy SF3B1 mutations in lung adenocarcinoma and other cancers.
Identifiants
pubmed: 33057152
doi: 10.1038/s41388-020-01507-5
pii: 10.1038/s41388-020-01507-5
pmc: PMC7790757
mid: NIHMS1634320
doi:
Substances chimiques
Phosphoproteins
0
RNA Splice Sites
0
RNA Splicing Factors
0
SF3B1 protein, human
0
SUGP1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
85-96Subventions
Organisme : NCI NIH HHS
ID : HHSN261201500003C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201400008C
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201500003I
Pays : United States
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