Idioma:

Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer

Nordentoft, Iver ; Lamy, Philippe ; Birkenkamp-Demtröder, Karin ; Shumansky, Karey ; Vang, Søren ; Hornshøj, Henrik ; Juul, Malene ; Villesen, Palle ; Hedegaard, Jakob ; Roth, Andrew ; Thorsen, Kasper ; Høyer, Søren ; Borre, Michael ; Reinert, Thomas ; Fristrup, Niels ; Dyrskjøt, Lars ; Shah, Sohrab ; Pedersen, Jakob Skou ; Ørntoft, Torben F.

Cell reports (Cambridge), 2014-06, Vol.7 (5), p.1649-1663 [Periódico revisado por pares]

United States: Elsevier Inc

Texto completo disponível

Citações Citado por

Enviar para

Título:
Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer
Autor: Nordentoft, Iver ; Lamy, Philippe ; Birkenkamp-Demtröder, Karin ; Shumansky, Karey ; Vang, Søren ; Hornshøj, Henrik ; Juul, Malene ; Villesen, Palle ; Hedegaard, Jakob ; Roth, Andrew ; Thorsen, Kasper ; Høyer, Søren ; Borre, Michael ; Reinert, Thomas ; Fristrup, Niels ; Dyrskjøt, Lars ; Shah, Sohrab ; Pedersen, Jakob Skou ; Ørntoft, Torben F.
Assuntos: APOBEC-1 Deaminase ; Carcinoma - genetics ; Carcinoma - pathology ; Class I Phosphatidylinositol 3-Kinases ; Clonal Evolution ; Cytidine Deaminase - genetics ; Cytidine Deaminase - metabolism ; DNA Repair ; DNA, Antisense - genetics ; Humans ; Phosphatidylinositol 3-Kinases - genetics ; Point Mutation ; Transcriptome ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - pathology
É parte de: Cell reports (Cambridge), 2014-06, Vol.7 (5), p.1649-1663
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Bladder cancer (or urothelial cell carcinoma [UCC]) is characterized by field disease (malignant alterations in surrounding mucosa) and frequent recurrences. Whole-genome, exome, and transcriptome sequencing of 38 tumors, including four metachronous tumor pairs and 20 superficial tumors, identified an APOBEC mutational signature in one-third. This was biased toward the sense strand, correlated with mean expression level, and clustered near breakpoints. A > G mutations were up to eight times more frequent on the sense strand (p < 0.002) in [ACG]AT contexts. The patient-specific APOBEC signature was negatively correlated to repair-gene expression and was not related to clinicopathological parameters. Mutations in gene families and single genes were related to tumor stage, and expression of chromatin modifiers correlated with survival. Evolutionary and subclonal analyses of early/late tumor pairs showed a unitary origin, and discrete tumor clones contained mutated cancer genes. The ancestral clones contained Pik3ca/Kdm6a mutations and may reflect the field-disease mutations shared among later tumors. [Display omitted] •A patient-specific APOBEC signature anticorrelates with DNA repair transcripts•A > G mutations are more frequent on the sense strand in [ACG]AT contexts•Chromatin modifiers mutate early in tumor evolution and point to poor prognosis•Mutations in mucosa surrounding tumors are defined by ancestral clones Deep sequencing can be used to investigate the mutational mechanism and the clonal content of bladder cancers. Nordentoft et al. now use a set of metachronous tumors, as well as single tumors, to document the presence of common mutational signatures (APOBEC and others) that correlate with reduced DNA repair. The authors examine the landscape of mutations in nonaggressive superficial bladder tumors and use these to define subclones pointing toward a unitary field lesion (alteration in the surrounding mucosa) as the origin of bladder tumors.
Editor: United States: Elsevier Inc
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Resultado 1 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer

United States: Elsevier Inc

Buscando em bases de dados remotas. Favor aguardar.