Mutational Analysis of Ionizing Radiation Induced Neoplasms
| Autor: | Katharine Yu, Amy L. Sherborne, Mamunur Rashid, Philip R. Davidson, Alice Nakamura, Jean L. Nakamura |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Ionizing
Neoplasms Radiation-Induced Carcinogenesis Medical Physiology DNA Mutational Analysis Gene Dosage Inbred C57BL medicine.disease_cause Cell morphology Transgenic Loss of heterozygosity Mice 0302 clinical medicine Neoplasms Radiation Ionizing 2.1 Biological and endogenous factors Aetiology lcsh:QH301-705.5 Exome sequencing Cancer Pediatric Genetics 0303 health sciences Mutation Radiation 3. Good health 030220 oncology & carcinogenesis Neurofibromatosis 1 Mice Transgenic Biology Gene dosage General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Rare Diseases Genes Neurofibromatosis 1 medicine Animals Gene 030304 developmental biology Animal Human Genome Mice Inbred C57BL Disease Models Animal lcsh:Biology (General) Radiation-Induced Genes Disease Models Biochemistry and Cell Biology |
| Zdroj: | Cell reports, vol 12, iss 11 Cell Reports, Vol 12, Iss 11, Pp 1915-1926 (2015) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.08.015 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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