کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2040972 1073138 2015 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mutational Analysis of Ionizing Radiation Induced Neoplasms
ترجمه فارسی عنوان
تجزیه و تحلیل موتاسیم نئوپلاسم های ناشی از اشعه یونیزدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Whole-exome sequencing of ionizing radiation induced malignancies reveals distinct mutational signatures
• Radiation-induced neoplasms from Nf1+/− mice are associated with specific copy-number alterations
• Ionizing radiation and genetic background each influence the mutational landscape

SummaryIonizing radiation (IR) is a mutagen that promotes tumorigenesis in multiple exposure contexts. One severe consequence of IR is the development of second malignant neoplasms (SMNs), a radiotherapy-associated complication in survivors of cancers, particularly pediatric cancers. SMN genomes are poorly characterized, and the influence of genetic background on genotoxin-induced mutations has not been examined. Using our mouse models of SMNs, we performed whole exome sequencing of neoplasms induced by fractionated IR in wild-type and Nf1 mutant mice. Using non-negative matrix factorization, we identified mutational signatures that did not segregate by genetic background or histology. Copy-number analysis revealed recurrent chromosomal alterations and differences in copy number that were background dependent. Pathway analysis identified enrichment of non-synonymous variants in genes responsible for cell assembly and organization, cell morphology, and cell function and maintenance. In this model system, ionizing radiation and Nf1 heterozygosity each exerted distinct influences on the mutational landscape.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 12, Issue 11, 22 September 2015, Pages 1915–1926
نویسندگان
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