Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

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Arquivos
art_GAO_Driver_Fusions_and_Their_Implications_in_the_Development_2018.PDF (3.64 MB)
Citações na Scopus
375
Tipo de produção
article
Data de publicação
2018
Editora
CELL PRESS
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
GAO, Qingsong
LIANG, Wen-Wei
FOLTZ, Steven M.
MUTHARASU, Gnanavel
JAYASINGHE, Reyka G.
CAO, Song
LIAO, Wen-Wei
REYNOLDS, Sheila M.
WYCZALKOWSKI, Matthew A.
YAO, Lijun
Autor de Grupo de pesquisa
Fusion Anal Working Grp
Canc Genome Atlas Res Network
Editores
Coordenadores
Organizadores
Citação
CELL REPORTS, v.23, n.1, p.227-238.e3, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/30114
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - IMT
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - ODS/03