scholarly journals P20.06: The experience with whole-genome array as a first-line cytogenetic test in invasive prenatal diagnosis

2018 ◽  
Vol 52 ◽  
pp. 192-192
Author(s):  
M. Hynek ◽  
M. Trkova ◽  
V. Becvarova ◽  
S. Brezinova ◽  
D. Smetanova ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Whole Genome ◽  
First Line ◽  
Genome Array

scholarly journals Whole-genome array as a first-line cytogenetic test in prenatal diagnosis

2015 ◽  
Vol 45 (4) ◽  
pp. 363-372 ◽  
Author(s):  
M. I. Srebniak ◽  
D. Van Opstal ◽  
M. Joosten ◽  
K. E. M. Diderich ◽  
F. A. T. de Vries ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Whole Genome ◽  
First Line ◽  
Genome Array

scholarly journals Clinical application of whole-genome array CGH during prenatal diagnosis: Study of 25 selected pregnancies with abnormal ultrasound findings or apparently balanced structural aberrations

2010 ◽  
Vol 3 (1) ◽  
pp. 24 ◽  
Author(s):  
Paola Evangelidou ◽  
Carolina Sismani ◽  
Marios Ioannides ◽  
Christodoulos Christodoulou ◽  
George Koumbaris ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Application ◽  
Array Cgh ◽  
Whole Genome ◽  
Ultrasound Findings ◽  
Structural Aberrations ◽  
Genome Array

scholarly journals Prenatal diagnosis of fetal multicystic dysplastic kidney via high-resolution whole-genome array

2016 ◽  
Vol 31 (10) ◽  
pp. 1693-1698 ◽  
Author(s):  
Fang Fu ◽  
Feifei Chen ◽  
Ru Li ◽  
Yongling Zhang ◽  
Min Pan ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
High Resolution ◽  
Multicystic Dysplastic Kidney ◽  
Whole Genome ◽  
Dysplastic Kidney ◽  
Genome Array

scholarly journals OC21.01: Whole-genome array as a first-tier cytogenetic test in routine prenatal diagnosis

2017 ◽  
Vol 50 ◽  
pp. 43-43
Author(s):  
M. Hynek ◽  
M. Trkova ◽  
V. Becvarova ◽  
H. Pekova ◽  
R. Mansfeldova ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Whole Genome ◽  
Genome Array

scholarly journals Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and whole-genome sequencing

2015 ◽  
Vol 35 (3) ◽  
pp. 299-301 ◽  
Author(s):  
M. J. Macera ◽  
A. Sobrino ◽  
B. Levy ◽  
V. Jobanputra ◽  
V. Aggarwal ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome

Towards Response Prediction Using Integrated Genomics in Chronic Lymphocytic Leukaemia: Results on 250 First-Line FCR Treated Patients from UK Clinical Trials

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1942-1942
Author(s):  
Ruth M Clifford ◽  
Pauline Robbe ◽  
Susanne Weller ◽  
Adele T Timbs ◽  
Michalis Titsias ◽  
...  
Keyword(s):  
Outcome Measure ◽  
Lymphocytic Leukaemia ◽  
Snp Array ◽  
Whole Genome ◽  
Line Treatment ◽  
First Line ◽  
Genome Wide ◽  
Recurrent Mutations ◽  
Integrated Genomics ◽  
First Line Treatment

Abstract Background: Major progress has been made in understanding disease biology and therapeutic options for patients with chronic lymphocytic leukaemia (CLL). Recurrent mutations have been discovered using next generation sequencing, but with the exception of TP53 disruption their potential impact on response to treatment is unknown. In order to address this question, we characterised the genomic landscape of 250 first-line chemo-immunotherapy treated CLL patients within UK clinical trials using targeted resequencing and whole-genome SNP array. Methods: We studied patients from two UK-based Phase II randomised controlled trials (AdMIRe and ARCTIC) receiving FCR-based treatment in a first-line treatment setting. A TruSeq Custom Amplicon panel (TSCA, Illumina) was designed targeting 10 genes recurrently mutated in CLL based on recent publications.Average sequencing depth was 2260X. The cumulated length of targets sequenced was 7.87 kb from 330 amplicons covering 160 exons. Alignment and variant calling included a combination of three pipelines to confidently detect SNVs, indels and low level frequency mutations. SNP array testing was performed using HumanOmni2.5-8 BeadChips, (Illumina) and data analysed using Nexus 6.1 Discovery Edition, Biodiscovery. We performed targeted resequencing and genome-wide SNP arrays using selected samples’ germline material to confirm somatic mutations (n=40). Univariate and multivariate analyses using minimal residual disease (MRD) as the outcome measure were performed for 220 of the 250 patients. Results: Pathogenic mutations were identified in 165 (66%) patients, totalling 268 mutations in 10 genes. ATM was the most frequently mutated gene affecting 67 patients (29%) followed by SF3B1 (n=56, 24%), NOTCH1 (n= 32, 14%), TP53 (n= 21, 9%), BIRC3 (n= 17, 7%) and XPO1 (n=14, 6%). Less frequently recurrent mutations were seen in SAMHD1 (n=8, 3%), MYD88 (n= 4, 2%), MED12 (n=7, 3%) and ZFPM2 (n=5, 2%). Integrating sequencing and array results increased the patients with one or more CLL driver mutation from 66% to 94%. As previously reported del17p and TP53 mutations are co-occurring and associate with MRD positivity in all cases (n=15, p=0.0002). We report on minor TP53 subclones in 11 patients (VAF 1-5%), 8 of whom have MRD data available and were also associated with MRD positivity. Deletions of 11q were present in 44 patients. These lesions always included ATM but not always BIRC3. Bialleleic disruption was present in ATM for 27 patients (significantly associated with MRD positivity) and in BIRC3 for 4 patients. Rather surprisingly, trisomy 12 (n=33) and NOTCH1 mutations (n=28) were associated with MRD negativity (p=0.006 and 0.097, respectively). Analysing clonal and subclonal mutations per gene revealed the majority of mutations in SF3B1 and BIRC3 were subclonal (65% and 87% respectively). In contrast almost all SAMHD1 and MYD88 mutations were clonally distributed. There was an association between NOTCH1 subclonal mutations and MRD negativity, compared to clonal mutations, but this difference was not seen in the remaining mutated genes. From our copy number data, the presence of subclones was associated with MRD positivity (p=0.05). Combining important lesions in a multiple logistic regression analysis to predict MRD positivity, bialleleic ATM disruption, together with TP53 disruption, were the strongest predictors, followed by SAMHD1, whereas BIRC3 monoalleleic mutations were a medium predictor for MRD negativity. Conclusion: This is the first integrated genome-wide analysis of the distribution and associations of CLL drivers, using targeted deep resequencing and whole genome SNP arrays in an FCR-based first-line treatment setting. We have shown subclonal and clonal mutation profiles in all patients. For patients with two or more CLL-associated mutations we have begun to unravel clonal hierarchies. We have developed a comprehensive model using MRD as an outcome measure and have found bialleleic ATM mutations and SAMHD1 disruption to strongly predict for MRD positivity. Using MRD status as a robust proxy for PFS not only enables us to confirm results of previous studies, but is advantageous also in considerably reducing the timeframe for results. Indeed, we suggest that MRD status should be assessed routinely in future studies to complement modern integrated genomics approaches. Disclosures Hillmen: Pharmacyclics, Janssen, Gilead, Roche: Honoraria, Research Funding.

OC20.06: Whole-genome array CGH in fetuses with major malformations: a Danish study

2012 ◽  
Vol 40 (S1) ◽  
pp. 41-41
Author(s):  
E. Vestergaard ◽  
R. Christensen ◽  
O. B. Petersen ◽  
I. Vogel
Keyword(s):  
Array Cgh ◽  
Whole Genome ◽  
Genome Array ◽  
Danish Study

scholarly journals Clinical implementation of whole-genome array CGH as a first-tier test in 5080 pre and postnatal cases

2011 ◽  
Vol 4 (1) ◽  
pp. 12 ◽  
Author(s):  
Sang-Jin Park ◽  
Eun Jung ◽  
Ran-Suk Ryu ◽  
Hyun Kang ◽  
Jung-Min Ko ◽  
...  
Keyword(s):  
Array Cgh ◽  
Whole Genome ◽  
Clinical Implementation ◽  
Genome Array
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