scholarly journals Somatic mutations in homologous recombination pathway predict favourable prognosis after immunotherapy across multiple cancer types

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Zaoqu Liu ◽  
Chunguang Guo ◽  
Jing Li ◽  
Hui Xu ◽  
Taoyuan Lu ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Somatic Mutations ◽  
Multiple Cancer ◽  
Homologous Recombination Pathway ◽  
Favourable Prognosis ◽  
Cancer Types ◽  
Recombination Pathway

Abstract 2750: Mutations on the homologous recombination pathway in 13 cancer types

2016 ◽  
Author(s):  
Joanne Xiu ◽  
Ryan Bender ◽  
Brian Abbott ◽  
Zoran Gatalica ◽  
Sandeep Reddy ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Homologous Recombination Pathway ◽  
Cancer Types ◽  
Recombination Pathway

scholarly journals Somatic mutations in homologous recombination pathway predict favorable prognosis after immunotherapy across multiple cancer types

2021 ◽  
Author(s):  
Zaoqu Liu ◽  
Jing Li ◽  
Chunguang Guo ◽  
Hui Xu ◽  
Taoyuan Lu ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Microsatellite Instability ◽  
Immune Checkpoints ◽  
Molecular Characteristics ◽  
Multiple Cancer ◽  
Independent Predictive Factor ◽  
Cancer Types ◽  
Cox Analysis ◽  
High Level ◽  
Recombination Pathway

Abstract Background: Homologous recombination (HR) pathway was recently implicated in modifying the tumor immune microenvironment and thus might serve as a candidate biomarker of immune checkpoint inhibitor (ICI) treatment. We aimed to comprehensively explore the clinical and molecular significance of HR mutations in ICI treatment across multiple cancer types.Methods: We analyzed the clinical and genomic data of 1,752 ICI-treated patients and 4,605 non-ICI-treated patients from cBioPortal, TCGA, and ICGC databases. The impacts of HR mutations on tumor mutations burden (TMB), neoantigen load (NAL), microsatellite instability (MSI), immune molecular characteristics, and multi-omics events were further investigated.Results: HR mutations corelated with improved prognosis in ICI-treated bladder cancer (BLCA), colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC), while in non-ICI cohorts, HR mutations were not associated with prognosis and even suggested unfavorable prognosis. Multivariable Cox analysis demonstrated HR mutations were an independent predictive factor for ICI treatment. Moreover, HR mutations could accurately predict high level of TMB, NAL, and MSI, and displayed the more prevalent incidence than TMB-high, NAL-high, and microsatellite instability-high (MSI-H), which indicated that HR mutations might be an ideal surrogate for TMB, NAL, and MSI estimation. HR mutations were also proven to correlate with the tumor microenvironment, immunity characteristics, immune checkpoints profiles, and substantial multi-omics alteration events.Conclusions: HR mutations are predictive of improved clinical outcomes in BLCA, CRC, and NSCLC treated with ICI instead of non-ICI, and might be a promising surrogate for TMB, NAL, and MSI estimation in ICI treatment.

scholarly journals Genomic Determinants of Homologous Recombination Deficiency across Human Cancers

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4572
Author(s):  
Tao Qing ◽  
Xinfeng Wang ◽  
Tomi Jun ◽  
Li Ding ◽  
Lajos Pusztai ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Copy Number ◽  
Somatic Mutations ◽  
Synthetic Lethality ◽  
Driver Mutations ◽  
Multiple Cancer ◽  
Clinical Biomarkers ◽  
Somatic Alterations ◽  
Cancer Types ◽  
Prostate Cancers

Germline BRCA1/2 mutations associated with HRD are clinical biomarkers for sensitivity to poly-ADP ribose polymerase inhibitors (PARPi) treatment in breast, ovarian, pancreatic, and prostate cancers. However, it remains unclear whether other mutations may also lead to HRD and PARPi sensitivity across a broader range of cancer types. Our goal was to determine the germline or somatic alterations associated with the HRD phenotype that might therefore confer PARPi sensitivity. Using germline and somatic genomic data from over 9000 tumors representing 32 cancer types, we examined associations between HRD scores and pathogenic germline variants, somatic driver mutations, and copy number deletions in 30 candidate genes involved in homologous recombination. We identified several germline and somatic mutations (e.g., BRCA1/2, PALB2, ATM, and ATR mutations) associated with HRD phenotype in ovarian, breast, pancreatic, stomach, bladder, and lung cancer. The co-occurrence of germline BRCA1 variants and somatic TP53 mutations was significantly associated with increasing HRD in breast cancer. Notably, we also identified multiple somatic copy number deletions associated with HRD. Our study suggests that multiple cancer types include tumor subsets that show HRD phenotype and should be considered in the future clinical studies of PARPi and synthetic lethality strategies exploiting HRD, which can be caused by a large number of genomic alterations.

Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells

2015 ◽  
Vol 116 (3) ◽  
pp. 358-365 ◽  
Author(s):  
Caroline V.M. Verhagen ◽  
Rosemarie de Haan ◽  
Floor Hageman ◽  
Tim P.D. Oostendorp ◽  
Annalisa L.E. Carli ◽  
...  
Keyword(s):  
Radiation Dose ◽  
Homologous Recombination ◽  
Tumor Cells ◽  
Parp Inhibitor ◽  
Homologous Recombination Pathway ◽  
Recombination Pathway

scholarly journals Crystal structure of RecR, a member of the RecFOR DNA-repair pathway, fromPseudomonas aeruginosaPAO1

2018 ◽  
Vol 74 (4) ◽  
pp. 222-230
Author(s):  
Shiyou Che ◽  
Yujing Chen ◽  
Yakun Liang ◽  
Qionglin Zhang ◽  
Mark Bartlam
Keyword(s):  
Crystal Structure ◽  
Dna Damage ◽  
Homologous Recombination ◽  
Analytical Ultracentrifugation ◽  
Repair Process ◽  
Asymmetric Unit ◽  
Homologous Recombination Pathway ◽  
Damage Repair ◽  
Important Regulator ◽  
Recombination Pathway

DNA damage is usually lethal to all organisms. Homologous recombination plays an important role in the DNA damage-repair process in prokaryotic organisms. Two pathways are responsible for homologous recombination inPseudomonas aeruginosa: the RecBCD pathway and the RecFOR pathway. RecR is an important regulator in the RecFOR homologous recombination pathway inP. aeruginosa. It forms complexes with RecF and RecO that can facilitate the loading of RecA onto ssDNA in the RecFOR pathway. Here, the crystal structure of RecR fromP. aeruginosaPAO1 (PaRecR) is reported.PaRecR crystallizes in space groupP6122, with two monomers per asymmetric unit. Analytical ultracentrifugation data show thatPaRecR forms a stable dimer, but can exist as a tetramer in solution. The crystal structure shows that dimericPaRecR forms a ring-like tetramer architectureviacrystal symmetry. The presence of a ligand in the Walker B motif of one RecR subunit suggests a putative nucleotide-binding site.

scholarly journals Increased sensitivity to ionizing radiation by targeting the homologous recombination pathway in glioma initiating cells

2014 ◽  
Vol 8 (8) ◽  
pp. 1603-1615 ◽  
Author(s):  
Yi Chieh Lim ◽  
Tara L. Roberts ◽  
Bryan W. Day ◽  
Brett W. Stringer ◽  
Sergei Kozlov ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Ionizing Radiation ◽  
Homologous Recombination Pathway ◽  
Glioma Initiating Cells ◽  
Increased Sensitivity ◽  
Recombination Pathway

scholarly journals Homologous recombination pathway may play a major role in high-LET radiation-induced DNA double-strand break repair

2014 ◽  
Vol 55 (suppl 1) ◽  
pp. i83-i84 ◽  
Author(s):  
A. Gerelchuluun ◽  
J. Zhu ◽  
F. Su ◽  
A. Asaithamby ◽  
D. J. Chen ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Homologous Recombination Pathway ◽  
Dna Double Strand Break ◽  
High Let Radiation ◽  
High Let ◽  
Radiation Induced ◽  
Recombination Pathway

scholarly journals Mutant TP53 disrupts age-related accumulation patterns of somatic mutations in multiple cancer types

2016 ◽  
Vol 209 (9) ◽  
pp. 376-380 ◽  
Author(s):  
Wensheng Zhang ◽  
Erik K. Flemington ◽  
Kun Zhang
Keyword(s):  
Somatic Mutations ◽  
Multiple Cancer ◽  
Age Related ◽  
Cancer Types

scholarly journals Development of Serous Ovarian Cancer is Associated with the Expression of Homologous Recombination Pathway Proteins

2014 ◽  
Vol 20 (4) ◽  
pp. 931-938 ◽  
Author(s):  
Qingqing Ye ◽  
Li Chen ◽  
Xiaolu Yin ◽  
Yuan Jie Charles Liu ◽  
Qunsheng Ji ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Serous Ovarian Cancer ◽  
Homologous Recombination Pathway ◽  
Recombination Pathway

Ovarian cancer: Status of homologous recombination pathway as a predictor of drug response

2016 ◽  
Vol 101 ◽  
pp. 50-59 ◽  
Author(s):  
Nicolas De Picciotto ◽  
Wulfran Cacheux ◽  
Arnaud Roth ◽  
Pierre O. Chappuis ◽  
S. Intidhar Labidi-Galy
Keyword(s):  
Ovarian Cancer ◽  
Homologous Recombination ◽  
Drug Response ◽  
Homologous Recombination Pathway ◽  
Recombination Pathway
Sign in / Sign up

Export Citation Format

Share Document