Por favor, use este identificador para citar o enlazar este ítem: https://observatorio.fm.usp.br/handle/OPI/30116
Título: Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas
Autor: KNIJNENBURG, Theo A.WANG, LinghuaZIMMERMANN, Michael T.CHAMBWE, NyashaGAO, Galen F.CHERNIACK, Andrew D.FAN, HuihuiSHEN, HuiWAY, Gregory P.GREENE, Casey S.LIU, YuexinAKBANI, RehanFENG, BinDONEHOWER, Lawrence A.MILLER, ChaseSHEN, YangKARIMI, MostafaCHEN, HaoranKIM, PoraJIA, PeilinSHINBROT, EveZHANG, ShaojunLIU, JianfangHU, HaiBAILEY, Matthew H.YAU, ChristinaWOLF, DeniseZHAO, ZhongmingWEINSTEIN, John N.LI, LeiDING, LiMILLS, Gordon B.LAIRD, Peter W.WHEELER, David A.SHMULEVICH, IlyaMONNAT JR., Raymond J.XIAO, YonghongWANG, Chen
Citación: CELL REPORTS, v.23, n.1, p.239-254.e6, 2018
Resumen: DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in similar to 20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structurebased analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy.
Aparece en las colecciones:

Artigos e Materiais de Revistas Científicas - FM/Outros
Outros departamentos - FM/Outros

Artigos e Materiais de Revistas Científicas - IMT
Instituto de Medicina Tropical - IMT

Artigos e Materiais de Revistas Científicas - LIM/14
LIM/14 - Laboratório de Investigação em Patologia Hepática

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar


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