Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 03 2022
25 03 2022
Historique:
received:
23
06
2021
accepted:
04
03
2022
entrez:
26
3
2022
pubmed:
27
3
2022
medline:
14
4
2022
Statut:
epublish
Résumé
Loss of expression or activity of the tumor suppressor PTEN acts similarly to an activating mutation in the oncogene PIK3CA in elevating intracellular levels of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), inducing signaling by AKT and other pro-tumorigenic signaling proteins. Here, we analyze sequence data for 34,129 colorectal cancer (CRC) patients, capturing 3,434 PTEN mutations. We identify specific patterns of PTEN mutation associated with microsatellite stability/instability (MSS/MSI), tumor mutational burden (TMB), patient age, and tumor location. Within groups separated by MSS/MSI status, this identifies distinct profiles of nucleotide hotspots, and suggests differing profiles of protein-damaging effects of mutations. Moreover, discrete categories of PTEN mutations display non-identical patterns of co-occurrence with mutations in other genes important in CRC pathogenesis, including KRAS, APC, TP53, and PIK3CA. These data provide context for clinical targeting of proteins upstream and downstream of PTEN in distinct CRC cohorts.
Identifiants
pubmed: 35338148
doi: 10.1038/s41467-022-29227-2
pii: 10.1038/s41467-022-29227-2
pmc: PMC8956741
doi:
Substances chimiques
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
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
1618Subventions
Organisme : NIGMS NIH HHS
ID : F30 GM142263
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006927
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108195
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA256234
Pays : United States
Informations de copyright
© 2022. The Author(s).
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