scholarly journals Concordance of copy number abnormality detection using SNP arrays and Multiplex Ligation-dependent Probe Amplification (MLPA) in acute lymphoblastic leukaemia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthew Bashton ◽  
Robin Hollis ◽  
Sarra Ryan ◽  
Claire J. Schwab ◽  
John Moppett ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Copy Number ◽  
Probe Design ◽  
Snp Arrays ◽  
Probe Coverage ◽  
Binary Segmentation ◽  
Platform Independence ◽  
Automated Pipeline ◽  
Copy Number Abnormality

AbstractIn acute lymphoblastic leukaemia, MLPA has been used in research studies to identify clinically relevant copy number abnormality (CNA) profiles. However, in diagnostic settings other techniques are often employed. We assess whether equivalent CNA profiles are called using SNP arrays, ensuring platform independence. We demonstrate concordance between SNP6.0 and MLPA CNA calling on 143 leukaemia samples from two UK trials; comparing 1,287 calls within eight genes and a region. The techniques are 99% concordant using manually augmented calling, and 98% concordant using an automated pipeline. We classify these discordant calls and examine reasons for discordance. In nine cases the circular binary segmentation (CBS) algorithm failed to detect focal abnormalities or those flanking gaps in IKZF1 probe coverage. Eight cases were discordant due to probe design differences, with focal abnormalities detectable using one technique not observable by the other. Risk classification using manually augmented array calling resulted in four out of 143 patients being assigned to a different CNA risk group and eight patients using the automated pipeline. We conclude that MLPA defined CNA profiles can be accurately mirrored by SNP6.0 or similar array platforms. Automated calling using the CBS algorithm proved successful, except for IKZF1 which should be manually inspected.

scholarly journals Clinical significance of recurrent copy number aberrations in B-lineage acute lymphoblastic leukaemia without recurrent fusion genes across age cohorts

2017 ◽  
Vol 178 (4) ◽  
pp. 583-587 ◽  
Author(s):  
Monica Messina ◽  
Sabina Chiaretti ◽  
Anna Lucia Fedullo ◽  
Alfonso Piciocchi ◽  
Maria Cristina Puzzolo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Clinical Significance ◽  
Lymphoblastic Leukaemia ◽  
Copy Number ◽  
Fusion Genes ◽  
Age Cohorts ◽  
Copy Number Aberrations ◽  
B Lineage

Acquired Genetic Abnormalities in Acute Lymphoblastic Leukaemia in Patients with Down Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 984-984
Author(s):  
Lyndal Kearney ◽  
Sharon W. Horsley ◽  
Caroline M. Bateman ◽  
David Gonzalez De Castro ◽  
Bryan D. Young ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Copy Number ◽  
Snp Array ◽  
Coding Region ◽  
Increased Risk ◽  
Genetic Abnormalities ◽  
Megakaryoblastic Leukaemia ◽  
Genetic Events

Abstract Children with Down syndrome (DS) have a 30 fold increased risk of developing leukaemia compared to their non-DS counterparts. While it is now known that cooperating mutations in the haemopoietic transcription factor GATA1 occur in all cases of acute megakaryoblastic leukaemia in Down syndrome patients, the additional genetic events which confer an increased risk of acute lymphoblastic leukaemia in Down syndrome (ALL-DS) are unknown. We initiated a search for mutations in the coding region of candidate genes including RAS, B-RAF, FLT3, KIT and JAK2 in a series of ALL-DS cases. No mutations were identified. We then carried out high resolution (Affymetrix 250K Nsp and 250K Sty) SNP array analysis of leukaemic blast cell DNA from 9 cases of ALL-DS, the majority of which had matched remission DNA. Overall, the whole and partial chromosome gains and losses were in agreement with the karyotype, but in all cases these were updated and refined. There were between 1 and 12 additional copy number alterations per case, with small focal deletions comprising 1 or 2 genes being more frequent than gains. The most common of these was a focal deletion of the CDKN2A gene (4 cases), all of which had either a partial deletion or copy number neutral LOH of the whole of 9p. The other most common focal deletions were of 12p13.3 (ETV6 gene) and 9p13.2 (PAX5), found in 2 cases each. Other regions affected included 3q13.2 (BTLA), 5q33.3 (EBF1), 13q14.2 (RB1) and 20p12.2 (including c20orf94), identified in 1 case each. These results indicate that the secondary genetic events in ALL-DS are similar to those for ALL overall (Mullighan et al., Nature446: 758–764, 2007). The number and pattern of submicroscopic genetic abnormalities more closely resembles that of ETV6-RUNX1 positive ALL than high hyperdiploid ALL (which includes acquired trisomy 21).

Assessment of Aneuploidy in Childhood Acute Lymphoblastic Leukaemia Using High Density Oligonucleotide Arrays.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 104-104
Author(s):  
Andrew G. Hall ◽  
Sarina Sulong ◽  
Christine Harrison ◽  
Lynne Minto ◽  
Nick Bown ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
X Chromosome ◽  
Lymphoblastic Leukaemia ◽  
Cytogenetic Analysis ◽  
Copy Number ◽  
Allelic Imbalance ◽  
Chromosome 21 ◽  
Gene Copy ◽  
Childhood Acute Lymphoblastic Leukaemia ◽  
Conventional Cytogenetic Analysis

Abstract Chromosomal copy number (CN) is an important prognostic index in childhood acute lymphoblastic leukaemia (ALL). High hyperdiploidy (51–65 chromosomes) is associated with a good prognosis and near haploidy (23–29) a poor outcome. Conventional cytogenetics produces accurate estimates of CN in the majority of cases but sometimes cytogenetic fails or the morphology of chromosomes in ALL is too poor for accurate identification. We have used single nucleotide polymorphism arrays (SNPA) to determine CN in 86 childhood ALL patients and have compared the results with conventional cytogenetic analysis. Comparison of hybridisation intensity to a reference set of 110 normal individuals was used to derive CN estimates on 34 samples obtained during remission from ALL. Twelve were analysed using GeneChip® Human Mapping 10K Array Xba 131 and 22 using Xba 142 version 2.0 arrays (Affymetrix). Gene copy number estimates for individual SNPs were averaged across the autosomes and X chromosome. Results confirmed that SNPA gave accurate estimates of CN in samples of normal cells. Analysis by SNPA was successful in all 86 presentation leukaemic samples. The results of conventional cytogenetic analysis was available in 75, 11 having a failed cytogenetic result. Estimates of CN were identical in 34 and within 1 chromosome in a further 28. High hyperdiploidy was observed in 28 cases. In 23 of these the cytogenetic and SNPA results were concordant, while in the remaining five cases with a normal (n=2) or a failed (n=3) cytogenetic result, there was evidence from interphase FISH analysis of a hidden, non-dividing high hyperdiploid clone. One patient had a SNPA result indicative of near-haploidy (23–29 chromosomes) and another low hypodiploidy (33–39 chromosomes) with the SNPA confirming the appropriate chromosomal losses. There was marked discordance in one case of near tetraploidy (a total underestimate of 33 chromosomes) but this was not unexpected as the four copies of most chromosomes comprised no allelic imbalance. Analysis of concordance for individual chromosomes showed that, of the 1679 chromosomes compared, there was concordance of copy number in 1517 (90%). The lowest concordance was for the X chromosome (79%) and chromosome 21 (77%). This level of discordance, at least for chromosome 21, may be explained by multiple copies with no allelic imbalance. For all other chromosomes the concordance level was above 80%. We have shown that SNPA can reliably estimate CN in high hyperdiploidy and near haploid cases. This is of great potential value for genome-wide screening in cases in which cytogenetics is not available. It also provides validation of the applicability of the technique for the analysis of DNA from the majority of tumour types which do not yield metaphases.

Screening for the P2RY8-CRLF2 fusion gene in childhood acute lymphoblastic leukaemia

2011 ◽  
Vol 223 (03) ◽  
Author(s):  
M Morak ◽  
R Joas ◽  
S Fischer ◽  
A Attarbaschi ◽  
G Mann ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Fusion Gene ◽  
Childhood Acute Lymphoblastic Leukaemia

Cerebral sinovenous thrombosis during asparaginase treatment

2003 ◽  
Vol 23 (03) ◽  
pp. 109-112
Author(s):  
A. Hirt ◽  
C. Zwicky ◽  
W.A. Wuillemin ◽  
K. Leibundgut
Keyword(s):  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Induction Treatment ◽  
Pathogenic Mechanisms ◽  
Cerebral Sinovenous Thrombosis ◽  
Haemorrhagic Infarction ◽  
Sinovenous Thrombosis

SummaryA boy (age: 71/12 years) with acute lymphoblastic leukaemia developed thrombosis of the sinus sagitalis superior with secondary haemorrhagic infarction while on induction treatment with vincristine, prednisone, and asparaginase. Based on this report, the potential pathogenic mechanisms are discussed with respect to congenital prothrombotic defects as well as to the role of antileukaemic treatment. Current hypotheses on mechanisms for thromboembolism in children and proposed prophylactic strategies are briefly summarized.

Sign in / Sign up

Export Citation Format

Share Document