scholarly journals Recurrent Somatic Chromosomal Abnormalities in Relapsed Extraocular Retinoblastoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 673
Author(s):  
Rosario Aschero ◽  
Jasmine H. Francis ◽  
Daiana Ganiewich ◽  
Soledad Gomez-Gonzalez ◽  
Claudia Sampor ◽  
...  
Keyword(s):  
High Frequency ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Comparative Genomic ◽  
Copy Number Alterations ◽  
Cgh Array ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Aggressive Tumor ◽  
Intraocular Retinoblastoma

Most reports about copy number alterations (CNA) in retinoblastoma relate to patients with intraocular disease and features of children with extraocular relapse remain unknown, so we aimed to describe the CNA in this population. We evaluated 23 patients and 27 specimens from 4 centers. Seventeen cases had extraocular relapse after initial enucleation and six cases after an initial preservation attempt. We performed an analysis of CNA and BCOR gene alteration by SNP array (Single Nucleotide Polymorfism array), whole-exome sequencing, IMPACT panel and CGH array (Array-based comparative genomic hybridization). All cases presented CNA at a higher prevalence than those reported in previously published studies for intraocular cases. CNA previously reported for intraocular retinoblastoma were found at a high frequency in our cohort: gains in 1q (69.5%), 2p (60.9%) and 6p (86.9%), and 16q loss (78.2%). Other, previously less-recognized, CNA were found including loss of 11q (34.8%), gain of 17q (56.5%), loss of 19q (30.4%) and BCOR alterations were present in 72.7% of our cases. A high number of CNA including 11q deletions, 17q gains, 19q loss, and BCOR alterations, are more common in extraocular retinoblastoma. Identification of these features may be correlated with a more aggressive tumor warranting consideration for patient management.

scholarly journals Clinical Utility and the Yield of Single Nucleotide Polymorphism Array in Prenatal Diagnosis of Fetal Central Nervous System Abnormalities

2021 ◽  
Vol 8 ◽  
Author(s):  
Meiying Cai ◽  
Hailong Huang ◽  
Liangpu Xu ◽  
Na Lin
Keyword(s):  
Central Nervous System ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Karyotype Analysis ◽  
Snp Array ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Pathogenic Cnvs

Applying single nucleotide polymorphism (SNP) array to identify the etiology of fetal central nervous system (CNS) abnormality, and exploring its association with chromosomal abnormalities, copy number variations, and obstetrical outcome. 535 fetuses with CNS abnormalities were analyzed using karyotype analysis and SNP array. Among the 535 fetuses with CNS abnormalities, chromosomal abnormalities were detected in 36 (6.7%) of the fetuses, which were consistent with karyotype analysis. Further, additional 41 fetuses with abnormal copy number variations (CNVs) were detected using SNP array (the detection rate of additional abnormal CNVs was 7.7%). The rate of chromosomal abnormalities, but not that of pathogenic CNVs in CNS abnormalities with other ultrasound abnormalities was significantly higher than that in isolated CNS abnormalities. The rates of chromosomal abnormalities and pathogenic CNVs in fetuses with spine malformation (50%), encephalocele (50%), subependymal cyst (20%), and microcephaly (16.7%) were higher than those with other isolated CNS abnormalities. The pregnancies for 36 cases with chromosomal abnormalities, 18 cases with pathogenic CNVs, and three cases with VUS CNVs were terminated. SNP array should be used in the prenatal diagnosis of fetuses with CNS abnormalities, which can enable better prenatal assessment and genetic counseling, and affect obstetrical outcomes.

scholarly journals Chromosomal Microarray Analysis of Fetuses with Nasal Bone Anomaly

2020 ◽  
Author(s):  
Xiaorui Xie ◽  
Xiaoqing Wu ◽  
Linjuan Su ◽  
Meiying Cai ◽  
Ying Li ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Nasal Bone ◽  
Chromosomal Microarray Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Fetal Nasal Bone ◽  
Structural Abnormalities

Abstract Objective: To explore the significance and value of fetal nasal bone anomaly (absence or hypoplasia) as indications of prenatal diagnosis.Methods: A total of 102 fetuses diagnosed with nasal bone absence or hypoplasia by ultrasonography underwent chorionic, amniotic, or umbilical cord blood puncture. Single nucleotide polymorphism microarray (SNP-array) was used to analyze fetal chromosomes.Results: Of the 102 fetuses with nasal bone absence or hypoplasia, 25 (24.5%) had chromosomal abnormalities, including 15 cases of trisomy 21, one trisomy 18 case, and 9 cases of other copy number variations. Among the 52 cases with isolated nasal bone absence or hypoplasia, 7(13.5%) had chromosomal abnormalities. In 50 cases, abnormal nasal bone with additional soft markers or structural abnormalities was observed, while 18 cases (36.0%) had chromosomal abnormalities, which were significantly higher than that among the fetuses with isolated nasal bone abnormality.Conclusion: Fetal nasal bone absence or hypoplasia can be used as an indication for prenatal diagnosis. The detection rate of chromosomal abnormalities increases with additional soft markers or structural abnormalities. This study demonstrates that fetal nasal bone absence or hypoplasia is associated with micro-deletions or micro-duplications of chromosomes. Application of single nucleotide polymorphism microarray (SNP-array) technology can reduce the rate of missed prenatal diagnoses.

scholarly journals SNP Array Profiling of Childhood Adrenocortical Tumors Reveals Distinct Pathways of Tumorigenesis and Highlights Candidate Driver Genes

2012 ◽  
Vol 97 (7) ◽  
pp. E1284-E1293 ◽  
Author(s):  
Eric Letouzé ◽  
Roberto Rosati ◽  
Heloisa Komechen ◽  
Mabrouka Doghman ◽  
Laetitia Marisa ◽  
...  
Keyword(s):  
Copy Number ◽  
Tp53 Mutation ◽  
Snp Array ◽  
Genetic Alterations ◽  
Chromosome 17 ◽  
Comparative Genomic ◽  
Copy Number Alterations ◽  
Wild Type ◽  
Driver Genes ◽  
Adrenocortical Tumors

Abstract Context: Childhood adrenocortical tumors (ACT) are rare malignancies, except in southern Brazil, where a higher incidence rate is associated to a high frequency of the founder R337H TP53 mutation. To date, copy number alterations in these tumors have only been analyzed by low-resolution comparative genomic hybridization. Objective: We analyzed an international series of 25 childhood ACT using high-resolution single nucleotide polymorphism arrays to: 1) detect focal copy number alterations highlighting candidate driver genes; and 2) compare genetic alterations between Brazilian patients carrying the R337H TP53 mutation and non-Brazilian patients. Results: We identified 16 significantly recurrent chromosomal alterations (q-value < 0.05), the most frequent being −4q34, +9q33-q34, +19p, loss of heterozygosity (LOH) of chromosome 17 and 11p15. Focal amplifications and homozygous deletions comprising well-known oncogenes (MYC, MDM2, PDGFRA, KIT, MCL1, BCL2L1) and tumor suppressors (TP53, RB1, RPH3AL) were identified. In addition, eight focal deletions were detected at 4q34, defining a sharp peak region around the noncoding RNA LINC00290 gene. Although non-Brazilian tumors with a mutated TP53 were similar to Brazilian tumors, those with a wild-type TP53 displayed distinct genomic profiles, with significantly fewer rearrangements (P = 0.019). In particular, three alterations (LOH of chromosome 17, +9q33-q34, and −4q34) were significantly more frequent in TP53-mutated samples. Finally, two of four TP53 wild-type tumors displayed as sole rearrangement a copy-neutral LOH of the imprinted region at 11p15, supporting a major role for this region in ACT development. Conclusions: Our findings highlight potential driver genes and cellular pathways implicated in childhood ACT and demonstrate the existence of different oncogenic routes in this pathology.

scholarly journals Whole Exome Sequencing Aids The Diagnosis of Fetal Skeletal Dysplasia

2020 ◽  
Author(s):  
Hui Tang ◽  
Qin Zhang ◽  
Linliang Yin ◽  
Jingjing Xiang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Skeletal Dysplasia ◽  
Clinical Symptoms ◽  
Single Nucleotide Polymorphism Array ◽  
Snp Array ◽  
Somatic Mosaicism ◽  
Single Nucleotide ◽  
Whole Exome

Abstract Background: Skeletal dysplasia is a complex group of bone and cartilage disorders with strong clinical and genetical heterogeneousity. Several types have prenatal phenotypes. And it is difficult to make a molecular diagnosis rapidly due to lacking family history and non-specific and limited clinical symptoms in utero. This study aims to diagnose 16 Chinese fetuses with skeletal dysplasia.Methods: Single nucleotide polymorphism-array (SNP-array) was performed in 12 of 16 samples. If no microdeletions or microreplications related to skeletal dysplasia were detected, whole-exome sequencing (WES) was adopted. And the last four cases only got whole-exome sequencing for analyzing copy number variants and single nucleotide variations at the same time.Results: Among the 16 cases, 12 patients received definitive diagnosis and we detected one deletion in DMD gene by SNP-array and 15 variants of 6 genes including FGFR3, COL1A1, COL1A2, ALPL, HSPG2 and DYNC2H1. 8 variants of COL1A1, COL1A2, ALPL and HSPG2 are novel. And somatic mosaicism in asymptomatic parent with mutations in COL1A1 or COL1A2 was observed.Conclusions: In general, our study expanded the prenatal phenotypes in Duchenne muscular dystrophy (DMD)/ Becker muscular dystrophy (BMD), found 8 novel variants and elucidated that the utilization of whole-exome sequencing improved the diagnosis yield of skeletal dysplasia and provided useful genetic counseling guidance for parents.

P–558 SNP array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: a systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
V Kamath ◽  
M P Chacko ◽  
M Mariano ◽  
R Kirubakaran ◽  
M S Kamath
Keyword(s):  
Systematic Review ◽  
Single Nucleotide Polymorphism ◽  
Prenatal Diagnosis ◽  
Diagnostic Accuracy ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Index Test ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Abstract Study question Does Single nucleotide polymorphism (SNP) array provide a diagnostic advantage over conventional karyotype in prenatal diagnosis for fetuses with an abnormal ultrasound? Summary answer SNP array in the prenatal setting provides an incremental diagnostic yield over karyotype and the diagnostic accuracy is comparable with combined SNP array and karyotype What is known already Single nucleotide polymorphism and comparative genomic hybridization based arrays (aCGH) are the two chromosomal microarray (CMA) platforms available. Guidelines which recommend offering CMA instead of karyotyping for prenatal diagnosis are mainly based on studies that compared aCGH with karyotype. There is a paucity of reviews that critically appraise the role of SNP array as a prenatal diagnostic tool. We decided to estimate the incremental yield of SNP array over karyotype in detecting chromosomal abnormalities, and to determine the diagnostic accuracy of SNP alone compared with SNP array and karyotype in combination for prenatal diagnosis in fetuses with an abnormal ultrasound. Study design, size, duration We conducted a systematic review of studies comparing SNP array with karyotype for prenatal diagnosis in fetuses with an abnormal ultrasound. We performed a literature search in the electronic databases of EMBASE, PubMed, CENTRAL, CDSR, SCOPUS and Web of science for relevant studies published in the English language between January1996 and May 2020. We also hand searched the referenced list of included studies and performed a google search for grey literature to identify potential studies. Participants/materials, setting, methods The study population was women undergoing prenatal diagnosis for abnormal fetal ultrasound. Studies in which SNP array and karyotyping had been used in fetuses with abnormal ultrasound and which allowed for a 2 x 2 data extraction table were included. We estimated the incremental yields for SNP array over karyotype. For determining the diagnostic accuracy, we considered SNP array alone as the index test and combined karyotype & SNP array as the reference standard. Main results and the role of chance We included six studies for quantitative analysis. After pooling results, incremental yield of SNP array over normal karyotype was 10% (95% confidence interval, CI 4 to 16%) in fetuses with abnormal ultrasound while incremental yield of karyotype over SNP array was 1% (95% CI 0 to 2%). The agreement between SNP array and karyotype was 92%. Variant of uncertain significance (VUS) rates ranged from 4–8%. For SNP array alone versus combined SNP array and conventional karyotype, pooled sensitivity and specificity was 0.96 (95% CI 0.91 to 0.99) and 1.00 (95% CI 0.99 to 1.00) respectively. The Area under curve (AUC) was 0.99 indicating the discriminating ability of the SNP array was very high to identify the fetus with chromosomal abnormalities. Limitations, reasons for caution Only studies published in English were included. There was some degree of heterogeneity in inclusion criteria for the included studies. Wider implications of the findings: The current study suggests SNP array alone can replace conventional karyotype for prenatal diagnosis in fetus with an abnormal ultrasound. Limitations to adoption of SNP testing might include the requirement of requisite expertise to interpret the results and counsel patients appropriately, especially with the propensity of SNPs to identify VUS. Trial registration number Not applicable

Loss of Heterozygosity in Childhood Acute Lymphoblastic Leukaemia Detected by Genome-Wide Microarray Single Nucleotide Polymorphism Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1088-1088
Author(s):  
Andrew G. Hall ◽  
Lisa C. Bloodworth ◽  
Linda A. Hogarth ◽  
Nick P. Bown ◽  
Julie A. Irving
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Loss Of Heterozygosity ◽  
Lymphoblastic Leukaemia ◽  
Poor Prognosis ◽  
Snp Array ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Abstract Loss of heterozygosity (LOH) is detectable in many forms of malignancy, including leukaemia, using techniques such as microsatellite analysis and comparative genomic hybridisation. However, these techniques are laborious and require the use of relatively large amounts of DNA if the whole genome is to be examined. Here we describe the use of oligonucleotide microarrays to characterise single nucleotide polymorphisms (SNPs) in lymphoblasts isolated from children with acute lymphoblastic leukaemia for the pan-genomic mapping of LOH with a resolution of 100–200kb. Results were compared with DNA obtained during remission and on relapse. Abnormalities were seen in 8 of 10 cases. The two cases with no abnormalities and one case which showed identical changes affecting whole chromosomes at relapse and presentation remain in remission 1–9 years following retreatment. The 7 cases which showed LOH not affecting entire chromosomes died following relapse, suggesting that partial LOH may be associated with a poor prognosis. In 4 cases LOH was only detectable at relapse suggesting that progressive LOH may be a cause of disease progression and/or drug resistance. This was supported by detailed analysis of one case in which LOH involving the glucocorticoid receptor (GR) was associated with mutation of the remaining allele. In cell line models the loss of a functional GR is associated with profound resistance to steroids. The most frequent abnormality detected in this series involved chromosome 9p. In each of the four cases where this was observed LOH included the INK4 locus. In three of the four cases INK4 loss was only observed at relapse (see figure), suggesting that this abnormality may be commonly associated with treatment failure, supporting previous reports that 9p abnormailities are associated with a poor prognosis. One case was reported as showing monosomy 20 as the sole cytogenetic aberration but LOH analysis identified 9p LOH and loss of 20q, with retention of heterozygocity for 20p. These findings strongly implicate unbalanced translocation der(9)t(9;20),-20 as described by Clark et al (Leukaemia, 2000, 14:241). Our observations demonstrate that SNP array analysis is a powerful new tool for the analysis of allelic imbalance and unbalanced translocations in leukaemic blasts.

scholarly journals De Novo Interstitial Deletion of 9q in a Pediatric Patient With Global Developmental Delay

2019 ◽  
Vol 6 ◽  
pp. 2329048X1984492
Author(s):  
Dennis Keselman ◽  
Ram Singh ◽  
Ninette Cohen ◽  
Zipora Fefer
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Snp Array ◽  
Interstitial Deletion ◽  
Global Developmental Delay ◽  
Comparative Genomic ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Basal Cell Nevus Syndrome ◽  
Ptch1 Gene

Cytogenomic microarray (CMA) methodologies, including array comparative genomic hybridization (aCGH) and single-nucleotide polymorphism-detecting arrays (SNP-array), are recommended as the first-tier test for the evaluation of imbalances associated with intellectual disability, autism, and multiple congenital anomalies. The authors report on a child with global developmental delay (GDD) and a de novo interstitial 7.0 Mb deletion of 9q21.33q22.31 detected by aCGH. The patient that the authors report here is noteworthy in that she presented with GDD and her interstitial deletion is not inclusive of the 9q22.32 locus that includes the PTCH1 gene, which is implicated in Gorlin syndrome, or basal cell nevus syndrome (BCNS), has not been previously reported among patients with a similar or smaller size of the deletion in this locus suggesting that the genomic contents in the identified deletion on 9q21.33q22.31 is critical for the phenotype.

scholarly journals Evaluation of chromosomal abnormalities and copy number variations in fetuses with ultrasonic soft markers

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Meiying Cai ◽  
Na Lin ◽  
Xuemei Chen ◽  
Meimei Fu ◽  
Nan Guo ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Snp Array ◽  
Copy Number Variations ◽  
Clinical Value ◽  
Single Nucleotide ◽  
Genetic Abnormalities ◽  
Significant Difference ◽  
Snp Array Analysis ◽  
Soft Marker

Abstract Background Some ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers. Methods Among 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis. Results Among 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups. Conclusions Genetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect pregnancy outcomes.

scholarly journals Array-comparative genomic hybridization in sporadic benign pheochromocytomas

2009 ◽  
Vol 16 (2) ◽  
pp. 505-513 ◽  
Author(s):  
Francien H van Nederveen ◽  
Esther Korpershoek ◽  
Ronald J deLeeuw ◽  
Albert A Verhofstad ◽  
Jacques W Lenders ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
High Frequency ◽  
Chromosomal Abnormalities ◽  
Neurofibromatosis Type ◽  
The Other ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Von Hippel Lindau ◽  
A Genome ◽  
High Resolution Analysis

Pheochromocytomas (PCC) are catecholamine-producing tumors arising from the adrenal medulla that occur either sporadically or in the context of hereditary cancer syndromes, such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease (VHL), neurofibromatosis type 1, and the PCC-paraganglioma syndrome. Conventional comparative genomic hybridization studies have shown loss of 1p and 3q in the majority of sporadic and MEN2-related PCC, and 3p and 11p loss in VHL-related PCC. The development of a submegabase tiling resolution array enabled us to perform a genome-wide high-resolution analysis of 36 sporadic benign PCC. The results show that there are two distinct patterns of abnormalities in these sporadic PCC, one consisting of loss of 1p with or without concomitant 3q loss in 20/36 cases (56%), the other characterized by loss of 3p with or without concomitant 11p loss in 11/36 (31%). In addition, we found loss of chromosome 22q at high frequency (35%), as well as the novel finding of high frequency chromosome 21q loss (21%). We conclude that there appear to be two subgroups of benign sporadic PCC, one of which has a pattern of chromosomal abnormalities that is comparable with PCC from patients with MEN2 and the other that is comparable with the PCC that arise in patients with VHL disease. In addition, genes on 21q and 22q might play a more important role in PCC pathogenesis than had been assumed thus far.

Sign in / Sign up

Export Citation Format

Share Document