scholarly journals Genetic Testing in Hereditary Breast and Ovarian Cancer Using Massive Parallel Sequencing

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Anna Ruiz ◽  
Gemma Llort ◽  
Carmen Yagüe ◽  
Neus Baena ◽  
Marina Viñas ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lower Cost ◽  
Pcr Amplification ◽  
Bioinformatic Analysis ◽  
Massive Parallel Sequencing ◽  
Diagnostic Strategy ◽  
Breast And Ovarian Cancer ◽  
Parallel Sequencing ◽  
Parallel Pyrosequencing ◽  
Generation Sequencing

High throughput methods such as next generation sequencing are increasingly used in molecular diagnosis. The aim of this study was to develop a workflow for the detection ofBRCA1andBRCA2mutations using massive parallel sequencing in a 454 GS Junior bench top sequencer. Our approach was first validated in a panel of 23 patients containing 62 unique variants that had been previously Sanger sequenced. Subsequently, 101 patients with familial breast and ovarian cancer were studied.BRCA1andBRCA2exon enrichment has been performed by PCR amplification using the BRCA MASTR kit (Multiplicom). Bioinformatic analysis of reads is performed with the AVA software v2.7 (Roche). In total, all 62 variants were detected resulting in a sensitivity of 100%. 71 false positives were called resulting in a specificity of 97.35%. All of them correspond to deletions located in homopolymeric stretches. The analysis of the homopolymers stretches of 6 bp or longer using the BRCA HP kit (Multiplicom) increased the specificity of the detection ofBRCA1andBRCA2mutations to 99.99%. We show here that massive parallel pyrosequencing can be used as a diagnostic strategy to test forBRCA1andBRCA2mutations meeting very stringent sensitivity and specificity parameters replacing traditional Sanger sequencing with a lower cost.

scholarly journals Contribution of Massive Parallel Sequencing to Diagnosis of Hereditary Ovarian Cancer in the Czech Republic

2019 ◽  
Vol 32 (Suppl 2) ◽  
Author(s):  
Jana Soukupová ◽  
Klára Lhotová ◽  
Petra Zemánková ◽  
Michal Vočka ◽  
Markéta Janatová ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Czech Republic ◽  
Massive Parallel Sequencing ◽  
Hereditary Ovarian Cancer ◽  
The Czech Republic ◽  
Parallel Sequencing

Cancer susceptibility mutations in individuals with breast and ovarian cancer using next-generation sequencing.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 1515-1515 ◽  
Author(s):  
Kenneth Offit ◽  
Kasmintan A Schrader ◽  
Kara Noelle Maxwell ◽  
Joseph Vijai ◽  
Steven Hart ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Cancer Susceptibility ◽  
Next Generation ◽  
Breast And Ovarian Cancer ◽  
Generation Sequencing

scholarly journals Design and validation of a next generation sequencing assay for hereditary breast and ovarian cancer

2015 ◽  
Author(s):  
Hyunseok P. Kang ◽  
Jared R Maguire ◽  
Clement S Chu ◽  
Imran S. Haque ◽  
Henry Lai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Single Nucleotide Variants ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Cancer Screen ◽  
Inherited Cancer ◽  
Increased Risk ◽  
Generation Sequencing

Hereditary breast and ovarian cancer syndrome, caused by a germline deleterious variant in the BRCA1 or BRCA2 genes, is characterized by an increased risk for breast, ovarian, pancreatic and other cancers. Identification of those who have a BRCA1/2 mutation is important so that they can take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. We describe the design and analytic validation of the Counsyl Inherited Cancer Screen, a next-generation-sequencing-based test to detect pathogenic variation in the BRCA1 and BRCA2 genes. We demonstrate that the test is capable of detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy-number variants (CNVs, also known as large rearrangements) with zero errors over a 96-sample validation set consisting of samples from cell lines and deidentified patient samples, including the well-characterized NA12878 sample from HapMap/1000 Genomes.

Breast and Ovarian Cancer Penetrance Estimates Derived From Germline Multiple-Gene Sequencing Results in Women

2017 ◽  
pp. 1-12 ◽  
Author(s):  
Allison W. Kurian ◽  
Elisha Hughes ◽  
Elizabeth A. Handorf ◽  
Alexander Gutin ◽  
Brian Allen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Cancer Risk ◽  
Case Control ◽  
Cancer Risks ◽  
Breast And Ovarian Cancer ◽  
Multiple Gene ◽  
Matched Case ◽  
Brca1 Brca2 ◽  
Generation Sequencing

Purpose Multiple-gene, next-generation sequencing panels are increasingly used to assess hereditary cancer risks of patients with diverse personal and family cancer histories. The magnitude of breast and ovarian cancer risk associated with many clinically tested genes, and independent of family cancer history, remains to be quantified. Methods We queried a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene ( APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CHEK2, MLH2, MSH2, MSH6, MUTYH, NBN, P14ARF, P16, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, and TP53) next-generation sequencing panel. Multivariable logistic regression models accounting for family history were used to examine the association between pathogenic mutations and breast or ovarian cancer. As a confirmatory approach, a matched case-control analysis was conducted, defining cases as patients with breast or ovarian cancer and controls as women without cancer. Results One or more pathogenic mutations were detected in 6,775 (7%) of 95,561 women. Eight genes ( ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53) were associated with breast cancer, with odds ratios (ORs) ranging from two-fold ( ATM: OR, 1.74; 95% CI, 1.46 to 2.07) to six-fold ( BRCA1: OR, 5.91; 95% CI, 5.25 to 6.67). Eleven genes ( ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, NBN, STK11, RAD51C, and RAD51D) were associated with ovarian cancer, with OR ranging from two-fold ( ATM: OR, 1.69; 95% CI, 1.19 to 2.40) to 40-fold ( STK11: OR, 41.9; 95% CI, 5.55 to 315). Multivariable models and matched case-control analyses yielded similar results. Conclusion Among nearly 100,000 clinically tested women, 7% carried a pathogenic mutation in one or more cancer-associated genes. Associated breast and ovarian cancer risks ranged from two- to 40-fold after controlling for family history. These results may inform cancer risk counseling.

scholarly journals Diagnostic Next-Generation Sequencing Panel for Hereditary Breast and Ovarian Cancer

2013 ◽  
Vol 24 ◽  
pp. iii13
Author(s):  
M.M. Menzel ◽  
T. Scheurenbrand ◽  
A. Sprecher ◽  
M. Schubach ◽  
F. Battke ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Next Generation ◽  
Breast And Ovarian Cancer ◽  
Generation Sequencing
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