Characterizing CDK12-Mutated Prostate Cancers.
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:
15 01 2021
15 01 2021
Historique:
received:
24
06
2020
revised:
17
08
2020
accepted:
23
09
2020
pubmed:
30
9
2020
medline:
14
8
2021
entrez:
29
9
2020
Statut:
ppublish
Résumé
Cyclin-dependent kinase 12 (CDK12) aberrations have been reported as a biomarker of response to immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Herein, we characterize CDK12-mutated mCRPC, presenting clinical, genomic, and tumor-infiltrating lymphocyte (TIL) data. Patients with mCRPC consented to the molecular analyses of diagnostic and mCRPC biopsies. Genomic analyses involved targeted next-generation (MiSeq; Illumina) and exome sequencing (NovaSeq; Illumina). TILs were assessed by validated immunocytochemistry coupled with deep learning-based artificial intelligence analyses including multiplex immunofluorescence assays for CD4, CD8, and FOXP3 evaluating TIL subsets. The control group comprised a randomly selected mCRPC cohort with sequencing and clinical data available. Biopsies from 913 patients underwent targeted sequencing between February 2015 and October 2019. Forty-three patients (4.7%) had tumors with CDK12 alterations. CDK12-altered cancers had distinctive features, with some revealing high chromosomal break numbers in exome sequencing. Biallelic CDK12-aberrant mCRPCs had shorter overall survival from diagnosis than controls [5.1 years (95% confidence interval (CI), 4.0-7.9) vs. 6.4 years (95% CI, 5.7-7.8); hazard ratio (HR), 1.65 (95% CI, 1.07-2.53); CDK12-altered mCRPCs have worse prognosis, with these tumors surprisingly being primarily enriched for CD4
Identifiants
pubmed: 32988971
pii: 1078-0432.CCR-20-2371
doi: 10.1158/1078-0432.CCR-20-2371
pmc: PMC7855716
mid: NIHMS1633723
doi:
Substances chimiques
CDK12 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinases
EC 2.7.11.22
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Comment
Langues
eng
Sous-ensembles de citation
IM
Pagination
566-574Subventions
Organisme : Prostate Cancer UK
ID : CEO13_2-002
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R21 CA099250
Pays : United States
Organisme : Cancer Research UK
ID : CRM108X-A25144
Pays : United Kingdom
Organisme : Department of Health
ID : ECMC-CRM064X
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Cancer Research UK
ID : CRUK/11/029
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C12540 A12829
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C12540/A13230
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C12540/A20447
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentOn
Informations de copyright
©2020 American Association for Cancer Research.
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