The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
03
06
2024
accepted:
15
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
In cancer research, RAS biology has been focused on only a handful of tumor types. While RAS genes have long been suspected as common contributors to a wide spectrum of cancer types, robust evidence is required to firmly establish their critical oncogenic significance. We present a data mining study using DepMap genome-wide CRISPR screening data, which provide substantial evidence to support the prominent pervasive oncogenic role and tissue-specific permissiveness of RAS gene mutations. Differential analysis of CRISPR effect scores identifies K- or N-RAS genes as the most differential gene in contrasts of (K-, N-, combined) RAS mutant versus wild-type cell lines across multiple tissue types. The distinguished tissue-specific pattern of KRAS vs. NRAS as top differential genes in subsets of tissue types and evidence from genome data supported the idea of KRAS- and NRAS-engaged tissue types. To our knowledge, this is the first report of prominent pervasive oncogenic role of RAS mutations revealed by gene dependency data that is beyond the current understanding of the oncogenic role of RAS genes and their well-known involved tissue types. Our findings strongly support RAS mutations as primary oncogenic drivers beyond traditionally recognized cancer types and offer insights into their tissue-specific permissiveness.
Identifiants
pubmed: 39455841
doi: 10.1038/s41598-024-76591-8
pii: 10.1038/s41598-024-76591-8
doi:
Substances chimiques
NRAS protein, human
EC 3.6.1.-
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
Membrane Proteins
0
KRAS protein, human
0
GTP Phosphohydrolases
EC 3.6.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25452Informations de copyright
© 2024. The Author(s).
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