Clonal Relatedness and Mutational Differences between Upper Tract and Bladder Urothelial Carcinoma.
Aged
Biomarkers, Tumor
/ genetics
Carcinoma, Transitional Cell
/ genetics
Clone Cells
/ metabolism
Colorectal Neoplasms, Hereditary Nonpolyposis
/ genetics
Female
Genetic Predisposition to Disease
/ genetics
Genomics
/ methods
High-Throughput Nucleotide Sequencing
/ methods
Humans
Male
Middle Aged
Mutation
Prospective Studies
Receptor, Fibroblast Growth Factor, Type 3
/ genetics
Tumor Suppressor Protein p53
/ genetics
Urinary Bladder
/ metabolism
Urinary Bladder Neoplasms
/ genetics
Urinary Tract
/ metabolism
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 2019
01 02 2019
Historique:
received:
27
06
2018
revised:
20
08
2018
accepted:
19
10
2018
pubmed:
26
10
2018
medline:
14
4
2020
entrez:
25
10
2018
Statut:
ppublish
Résumé
To investigate genomic differences between urothelial carcinomas of the upper tract (UTUC) and bladder (UCB), with a focus on defining the clonal relatedness of temporally distinct tumors. We prospectively sequenced tumors and matched germline DNA using targeted next-generation sequencing methods. The cohort included 195 UTUC patients and 454 UCB patients. For a subgroup of 29 patients with UTUC and a history of a subsequent UCB, both tumors were analyzed to assess their clonal relatedness. With the progression to higher UTUC clinical state, there were fewer alterations in the RTK/RAS pathway but more alterations in TP53/MDM2. Compared with UCB, UTUC and UCB exhibit significant differences in the prevalence of common genomic alterations. In individual patients with a history of both tumors, UCB and UTUC were always clonally related. Genomic characterization of UTUC provides information regarding the risk of bladder recurrence and can identify tumors associated with Lynch syndrome.
Identifiants
pubmed: 30352907
pii: 1078-0432.CCR-18-2039
doi: 10.1158/1078-0432.CCR-18-2039
pmc: PMC6359971
mid: NIHMS1510880
doi:
Substances chimiques
Biomarkers, Tumor
0
Tumor Suppressor Protein p53
0
FGFR3 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 3
EC 2.7.10.1
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
967-976Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221745
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA182587
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2018 American Association for Cancer Research.
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