A case report of multiple primary prostate tumors with differential drug sensitivity.
Aged
Androgen Antagonists
/ therapeutic use
Drug Resistance, Neoplasm
Gene Deletion
Humans
Male
Mutation
Neoadjuvant Therapy
Neoplasm Grading
Neoplasms, Multiple Primary
/ drug therapy
PTEN Phosphohydrolase
/ deficiency
Prostatic Neoplasms
/ drug therapy
Sequence Analysis, DNA
Tumor Suppressor Protein p53
/ deficiency
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 02 2020
13 02 2020
Historique:
received:
12
06
2019
accepted:
23
01
2020
entrez:
15
2
2020
pubmed:
15
2
2020
medline:
28
4
2020
Statut:
epublish
Résumé
Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses of PTEN and TP53. The PTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies of PTEN and TP53, while the Gleason 7 PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer.
Identifiants
pubmed: 32054861
doi: 10.1038/s41467-020-14657-7
pii: 10.1038/s41467-020-14657-7
pmc: PMC7018822
doi:
Substances chimiques
Androgen Antagonists
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
837Subventions
Organisme : NCI NIH HHS
ID : HHSN261200800001E
Pays : United States
Organisme : NCI NIH HHS
ID : ZIA BC011679
Pays : United States
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