Molecular characteristics and clinical outcomes of patients with Neurofibromin 1-altered metastatic colorectal cancer.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
13
08
2021
accepted:
08
10
2021
revised:
01
10
2021
pubmed:
4
11
2021
medline:
17
2
2022
entrez:
3
11
2021
Statut:
ppublish
Résumé
Loss-of-function alterations of Neurofibromin 1 (NF1) activate RAS, a driver of colorectal cancer. However, the clinical implications of NF1 alterations are largely unknown. We performed a comprehensive molecular profiling of NF1-mutant colorectal cancer using data from 8150 patients included in a dataset of commercial CLIA-certified laboratory (Caris Life Sciences). In addition, NF1 expression levels were tested for associations with clinical outcomes using data from 431 patients in the CALGB/SWOG 80405 trial. In the Caris dataset, 2.2% of patients had pathogenic or presumed pathogenic NF1 mutations. NF1-mutant tumors more frequently harbored PIK3CA (25.0% vs. 16.7%) and PTEN mutations (24.0% vs. 4.2%) than wild type tumors. Gene set enrichment analysis revealed that MAPK and PI3K pathway signatures were enriched in NF1-mutant tumors. In the CALGB/SWOG 80405 cohort, low NF1 expression was associated with poor prognosis, and high NF1 expression was associated with better efficacy of cetuximab than bevacizumab. Together, we revealed concurrent genetic alterations in the PI3K pathways in NF1-mutant tumors, suggesting the need to simultaneously block MAPK and PI3K pathways in treatment. The potential of NF1 alteration as a novel biomarker for targeted therapy was highlighted, warranting further investigations in clinical settings.
Identifiants
pubmed: 34728807
doi: 10.1038/s41388-021-02074-z
pii: 10.1038/s41388-021-02074-z
pmc: PMC8738154
mid: NIHMS1759155
doi:
Substances chimiques
Neurofibromin 1
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
260-267Subventions
Organisme : NCI NIH HHS
ID : U10 CA180821
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233373
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180882
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233163
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180888
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180819
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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