Copy Number Variations of DNA Repair Genes and the Age-Related Cataract: Jiangsu Eye Study

2013 ◽  
Vol 54 (2) ◽  
pp. 932 ◽  
Author(s):  
Jin Jiang ◽  
Jing Zhou ◽  
Yong Yao ◽  
Rongrong Zhu ◽  
Congkai Liang ◽  
...  
Keyword(s):  
Dna Repair ◽  
Copy Number ◽  
Copy Number Variations ◽  
Dna Repair Genes ◽  
Age Related ◽  
Repair Genes

Copy number variations in AR-associated and DNA repair genes from plasma cell-free DNA of metastatic CRPC patients.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
Ratish Gambhira ◽  
Elisa M. Ledet ◽  
Aryeneesh Dotiwala ◽  
Diptasri Mandal ◽  
A. Oliver Sartor
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Progression ◽  
Copy Number ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Dna Repair Genes ◽  
Prostate Cancer Progression ◽  
Free Dna ◽  
Repair Genes

281 Background: Cell-free DNA (cfDNA) present in the plasma of advanced cancer patients can reflect tumor related genetic alterations. Recent data suggests copy number variations (CNVs) in AR-associated and DNA repair pathway genes play a potential role in prostate cancer progression. Here, we performed sequencing of cfDNA from 13 mCRPC patients to evaluate its potential in elucidating tumor related genetic variations. The long-term goal of our project is to correlate cfDNA derived genetic alterations with prostate cancer progression and/or therapeutic resistance/responses. Methods: cfDNA was isolated from 13 advanced mCRPC patient plasma samples using the Qiagen circulating nucleic acid kit. 100ng of cfDNA was utilized for library construction; and the libraries were paired-end sequenced on the Illumina HiSeq 2000. The resulting data was analyzed using the GATK best practices bioinformatics pipeline and the visualized using the SNP & Variation Suite v8.x. Results: The bioanalyzer profiles of cfDNA derived from mCRPC patients is highly fragmented with an average fragment size of 306-605bp. Although, several CNVs were found across the genome, we focused analysis on CNVs related to AR associated and DNA repair genes. Our preliminary analysis of cfDNA, despite low sequencing depth, shows full or partial amplifications in AR (13/13), and other genes including FOXA1, NCOR1, NCOR2 and/or PIK3CA (7/13) and NCOR2 (10/13). For DNA repair genes partial/full amplifications were present in BRAC1, BRAC2, ATM, CDK12, MLH1 and/or MSH2 (7/13). Deletions are less reliably detected in the highly fragmented cfDNA. The majority of these CNVs have been reported in the WGS studies from metastatic CRPC tissue derived genomic DNA (cBioPortal). We are currently validating cfDNA genomic alterations by comparing it to germ line DNA derived via qPCR. Conclusions: Our preliminary study indicates that AR and DNA repair related genetic alterations could be found in the cfDNA derived from metastatic CRPC patients. This warrants more detailed examination of these cfDNA genetic alterations for identifying clinically relevant issues in mCRPC patients.

Expression of DNA repair genes in lens cortex of age-related cortical cataract

2017 ◽  
Vol 102 (2) ◽  
pp. 219-223 ◽  
Author(s):  
Yong Wang ◽  
Junfang Zhang ◽  
Jian Wu ◽  
Huaijin Guan
Keyword(s):  
Dna Repair ◽  
Dna Repair Genes ◽  
Cortical Cataract ◽  
Age Related ◽  
Repair Genes

A Gynecologic Oncology Group study of frequent copy number aberrations in DNA repair genes and other genomic regions in stage I serous ovarian cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16504-e16504
Author(s):  
T. Pejovic ◽  
D. P. Gaile ◽  
K. M. Darcy ◽  
S. Liu ◽  
L. Shepherd ◽  
...  
Keyword(s):  
Dna Repair ◽  
Copy Number ◽  
Tissue Bank ◽  
Stage I ◽  
Gynecologic Oncology Group ◽  
Dna Repair Genes ◽  
Copy Number Aberrations ◽  
Ovarian Cancers ◽  
Genomic Regions ◽  
Repair Genes

e16504 Background: A proof of principle array-based comparative genomic hybridization (aCGH) analysis was performed in archival formalin-fixed and paraffin-embedded (FFPE) stage I ovarian cancers (EOC) to determine if frequent (>40%) copy number aberrations (CNAs) can be detected in DNA repair genes including the Fanconi anemia complementation group (FANC) and RAD51 families compared with the rest of the genome. Methods: Tumor DNA was isolated from 22 serous cancers from the GOG-175 virtual tissue bank. RPCI 19K BAC arrays were hybridized (GeneTAC HybStation) and scanned (Gene Pix 4200AL Laser Scanner). Spot fluorescence values were quantified using ImaGene, vetted for quality and loess corrected with adjustments for chip-specific spatial effects. The genome was segmented to identify regions with common copy number means (DNAcopy software). Posterior aberration probabilities for the regions were obtained using CGHcall and data was visualized and annotated using iGenomicViewer in R. Results: Several genes associated with the Fanconi DNA-damage response pathway were frequently altered in stage I serous ovarian carcinomas. A RAD51 homology DMC1 was amplified in 55% of the specimens. Genomic losses were observed in FANC-D1 (BRCA2), and RAD51L3 in 41%, and 27% of specimens, respectively. In contrast, frequent genomic losses or gains involved 13q33.1; 13 q21.31; 17p12; 17q22; 18q12.3; 9p11.2; 9p22.2–22.3; 9q33.1; 8p23.2; 21q21.3; and 5q14.2; or 8q24.3; 3q29; 12p11.1; 17q25.1; 17q25.3; 20q13.33; 20q11.21; 20q11.23; 19p13.13; and 19p13.2, respectively. Conclusions: The GOG-0175 virtual tissue bank yielded high quality DNA for detecting and mapping CNAs in archival FFPE specimens with high resolution. Frequent genomic losses and gains were observed in DNA repair genes and other genomic regions in stage I serous ovarian cancer which may promote genomic instability, resistance, metastasis and aggressiveness of this disease. No significant financial relationships to disclose.

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