Proteogenomic Analysis of Salivary Adenoid Cystic Carcinomas Defines Molecular Subtypes and Identifies Therapeutic Targets.
Adult
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Biomarkers, Tumor
/ antagonists & inhibitors
Carcinoma, Adenoid Cystic
/ diagnosis
Cohort Studies
Female
Humans
Male
Middle Aged
Molecular Targeted Therapy
/ methods
Mutation
Proteogenomics
RNA-Seq
Salivary Gland Neoplasms
/ diagnosis
Salivary Glands
/ pathology
Up-Regulation
Exome Sequencing
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
31
03
2020
revised:
10
08
2020
accepted:
04
11
2020
pubmed:
12
11
2020
medline:
19
1
2022
entrez:
11
11
2020
Statut:
ppublish
Résumé
Salivary gland adenoid cystic carcinoma (ACC) has heterogeneous clinical behavior. Currently, all patients are treated uniformly, and no standard-of-care systemic therapy exists for metastatic ACC. We conducted an integrated proteogenomic analyses of ACC tumors to identify dysregulated pathways and propose a classification with therapeutic implications. RNA/DNA sequencing of 54 flash-frozen salivary ACCs and reverse phase protein array (RPPA) in 38 specimens were performed, with validation by Western blotting and/or IHC. Three independent ACC cohorts were used for validation. Both unbiased RNA sequencing (RNA-seq) and RPPA analysis revealed two molecular subtypes: ACC-I (37%) and ACC-II (63%). ACC-I had strong upregulation of Cooccurrence of multiple actionable protein/pathways alterations in each subtype indicates unique therapeutic vulnerabilities and opportunities for optimal combination therapy for this understudied and heterogeneous disease.
Identifiants
pubmed: 33172898
pii: 1078-0432.CCR-20-1192
doi: 10.1158/1078-0432.CCR-20-1192
pmc: PMC7854509
mid: NIHMS1645731
doi:
Substances chimiques
Biomarkers, Tumor
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
852-864Subventions
Organisme : NIDCR NIH HHS
ID : HHSN268200900039C
Pays : United States
Organisme : NCI NIH HHS
ID : K99 CA240689
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
©2020 American Association for Cancer Research.
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