scholarly journals Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer

2015 ◽  
Vol 3 (5) ◽  
pp. 459-466 ◽  
Author(s):  
Yosuke Hirotsu ◽  
Hiroshi Nakagomi ◽  
Ikuko Sakamoto ◽  
Kenji Amemiya ◽  
Toshio Oyama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Panel Analysis ◽  
Breast And Ovarian Cancer ◽  
Repair Genes ◽  
Multigene Panel

scholarly journals Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Simone da Costa e Silva Carvalho ◽  
Nathalia Moreno Cury ◽  
Danielle Barbosa Brotto ◽  
Luiza Ferreira de Araujo ◽  
Reginaldo Cruz Alves Rosa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Gene Panel ◽  
Brazilian Population ◽  
Dna Repair Genes ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Germline Variants ◽  
Repair Genes ◽  
Syndrome Analysis

Single nucleotide polymorphisms (SNPs) of hOGG1 and XRCC1 DNA repair genes and the risk of ovarian cancer in Polish women

Tumor Biology ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 9457-9463 ◽  
Author(s):  
Magdalena M. Michalska ◽  
Dariusz Samulak ◽  
Hanna Romanowicz ◽  
Jan Bieńkiewicz ◽  
Maciej Sobkowski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Single Nucleotide Polymorphisms ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Repair Genes

Abstract 1783: Examination of the chemoresistant subpopulation in ovarian cancer identifies DNA repair genes contributing to survival after primary therapy.

2013 ◽  
Author(s):  
Britt K. Erickson ◽  
Adam D. Steg ◽  
Zach C. Dobbin ◽  
Ashwini A. Katre ◽  
Ronald D. Alvarez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Primary Therapy ◽  
Dna Repair Genes ◽  
Repair Genes

Comparison of germline mutations in African American and Caucasian men with metastatic prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5568-5568
Author(s):  
Elisa Marie Ledet ◽  
Ellen Jaeger ◽  
Whitley Hatton ◽  
Marcus W. Moses ◽  
Alexandra Sokolova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Dna Repair ◽  
African American ◽  
Family History ◽  
Metastatic Prostate Cancer ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Brca Mutations ◽  
Repair Genes

5568 Background: The relevance of germline mutations in metastatic prostate cancer is well established; however, comparison of germline genetics in African American (AA) versus Caucasian (CA) men with metastatic prostate cancer (PCa) is limited. Methods: Germline data from self-identified AA and CA metastatic PCa patients (pts) were collected from 5 academic cancer centers. Various commercial cancer-specific germline testing panels were used to evaluate 12-86 genes. Pathogenic (P) or likely pathogenic (LP) mutations, and variants of unknown significance (VUS), were reported according to ACMG guidelines. Self-reported family history (FH) was annotated for 99% of pts. Statistical analyses included Chi-squared and Fischer’s exact tests. Results: A total of 821 metastatic PCa pts were assessed: 152 AAs and 669 CAs. For P/LP alterations, AAs had a frequency of 11.2% (17/152) as compared to a frequency of 14.6% (98/669) in CAs (p = 0.302). AA pts were more likely to have a VUS than CA pts, 61% vs 43% respectively (OR = 2.09, 95%CI [1.45, 2.99], p < 0.001). BRCA mutations were similar between races, but AA were more likely to have a BRCA1 P/LP alteration (OR = 6.00, 95% CI [1.33, 27.09], p = 0.025). AA pts were less likely to have a P/LP alteration in a non-BRCA gene (OR = 0.34, 95% CI [0.15, 0.80], p = 0.013). Among DNA repair genes, there were no significant difference between AA and CA pts (p = 0.574); however, there was a trend toward AA pts having fewer P/LP alteration in a non-BRCA DNA repair genes (OR = 0.26, 95% CI [0.06, 1.08], p = 0.071). In pts with >1 first degree relative (FDR) with ovarian cancer, P/LP germline alterations were more likely in CAs (OR = 2.33, 95% CI [1.05, 5.17], p = 0.043); but there were no significant differences in AAs (p = 0.098). Those with >2 FDRs with PCa were more likely to have a P/LP change in CAs (OR = 2.32, 95% CI [1.04, 5.15], p = 0.043), but there were no difference in AAs (p = 0.700). In pts with ≥2 FDRs with breast cancer, P/LP germline alterations were more likely in both AAs (OR = 9.36, 95% CI [1.72, 50.84], p = 0.019) and CAs (OR = 3.92, 95% CI [1.79, 8.59], p = 0.001). Conclusions: We did not observe a difference in the overall frequency of germline P/LP alterations between AA and CA men with metastatic PCa but VUSs were more common in AA men. These AA men have an overall frequency of BRCA mutations similar to CA men; however, BRCA1 mutations were more prevalent in these AAs. Non-BRCA P/LP mutations are significantly less frequent in AA pts. A positive family history of >2 FDRs with breast cancer was associated with P/LP alterations in both AA and CA pts.

MP57-01 GERMLINE MUTATIONS IN DNA REPAIR GENES ARE SIGNIFICANTLY ENRICHED IN LETHAL PROSTATE CANCER AND ARE ASSOCIATED WITH DISEASE SURVIVAL

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Rong Na ◽  
S. Lilly S. Lilly ◽  
Misop Han ◽  
Hongjie Yu ◽  
Deke Jiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Repair Genes ◽  
Lethal Prostate Cancer

Germline DNA repair mutations in metastatic castration-resistant prostate cancer: Therapy response and applicability of circulating tumor DNA.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Werner J. Struss ◽  
Matti Annala ◽  
Evan W Warner ◽  
Kevin Beja ◽  
Gillian Vandekerkhove ◽  
...  
Keyword(s):  
Dna Repair ◽  
Targeted Therapy ◽  
Gene Loss ◽  
Germline Mutations ◽  
Circulating Tumor Dna ◽  
Dna Repair Genes ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Repair Genes ◽  
Tumor Dna

140 Background: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to Androgen Receptor (AR) targeted therapy. The aim of this study was to determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies, and secondly to establish whether biallelic DNA-repair gene loss is detectable in matched circulating tumor DNA (ctDNA). Methods: We recruited 319 mCRPC patients and performed targeted germline sequencing of 22 DNA repair genes. In affected patients, matched plasma ctDNA was also sequenced. Prostate-specific antigen response and progression were assessed in relation to initial androgen deprivation therapy (ADT) and subsequent therapy for mCRPC using Kaplan-Meier analysis. Results: 24/319 (7.5%) patients had deleterious germline mutations, with BRCA2 (n = 16), PALB2 (n = 2) and CDK12 (n = 2) being the most frequent. Patients (n = 22) with mutations in genes linked to homologous recombination were heterogeneous at initial presentation but after starting ADT progressed to mCRPC with a median time of 12.3 months (95% CI 5.1-18.4). The median time to progression on first and second line AR-targeted therapy in the mCRPC setting was 3.2 months (95% CI 1.9-4.4) and 1.0 month (95% CI 0.8-1.1), respectively. For patients receiving chemotherapy as their initial therapy for mCRPC (n = 8) the median PFS was 7.5 months (95% CI 6.5-8.2). 10/11 evaluable patients with germline BRCA2 mutations had somatic deletion of the intact allele in ctDNA. Conclusions: mCRPC patients with germline DNA repair defects exhibit transient responses to AR-targeted therapy. Biallelic gene loss was robustly detected in ctDNA suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy.

Expression of DNA repair genes in ovarian cancer samples: Biological and clinical considerations

2011 ◽  
Vol 47 (7) ◽  
pp. 1086-1094 ◽  
Author(s):  
M. Ganzinelli ◽  
P. Mariani ◽  
D. Cattaneo ◽  
R. Fossati ◽  
R. Fruscio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Dna Repair Genes ◽  
Clinical Considerations ◽  
Repair Genes

scholarly journals Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma

2017 ◽  
Vol 12 (11) ◽  
pp. 1673-1678 ◽  
Author(s):  
Erin M. Parry ◽  
Dustin L. Gable ◽  
Susan E. Stanley ◽  
Sara E. Khalil ◽  
Valentin Antonescu ◽  
...  
Keyword(s):  
Dna Repair ◽  
Lung Adenocarcinoma ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Repair Genes

scholarly journals DNA repair genes are selectively mutated in diffuse large B cell lymphomas

2013 ◽  
Vol 210 (9) ◽  
pp. 1729-1742 ◽  
Author(s):  
Noel FCC de Miranda ◽  
Roujun Peng ◽  
Konstantinos Georgiou ◽  
Chenglin Wu ◽  
Elin Falk Sörqvist ◽  
...  
Keyword(s):  
Dna Repair ◽  
B Cell ◽  
Genomic Instability ◽  
Novel Mutation ◽  
B Cell Lymphoma ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
B Cell Lymphomas ◽  
Repair Genes ◽  
Large B Cell

DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.

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