کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2040350 1073107 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer
ترجمه فارسی عنوان
زمینه موتاساری و توسعه کلونال در سرطانهای زودرس و بعد از آن
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• 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

SummaryBladder 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 7, Issue 5, 12 June 2014, Pages 1649–1663
نویسندگان
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