Cytogenetic, fluorescence in situ hybridization, and genomic array characterization of chronic myeloid leukemia with cryptic BCR-ABL1 fusions

Shao, Lina; Miller, Sue; Keller‐Ramey, Jennifer; Zhang, Yang; Roulston, Diane

doi:10.1016/j.cancergen.2015.04.006

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…However, for CML patients in the chronic phase (CP), deletion of ABL1-BCR did not result in poor response to imatinib or lower rates of either complete cytogenetic or major molecular responses ( Quintas-Cardama et al, 2011 ; Svabek et al, 2018 ). While it suggested that clonal copy number aberrations remain a hallmark of disease progression ( Shao et al, 2015 ), the mechanism of the disease progression has not been fully illustrated. Due to the relatively small sample size in this study, the relationship between CML phase and CNVs cannot be further studied.…”

Section: Discussionmentioning

confidence: 99%

Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update

Zhang

Wang

et al. 2021

Front. Genet.

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BackgroundSubmicroscopic segmental imbalances detected by array-comparative genomic hybridization (array-CGH) were discovered to be common in chronic myeloid leukemia (CML) patients with t(9;22) as the sole chromosomal anomaly. To confirm the findings of the previous study and expand the investigation, additional CML patients with t(9;22) as the sole chromosomal anomaly were recruited and copy number variants (CNVs) were searched for.MethodsKaryotyping tests were performed on 106 CML patients during January 2010–September 2019 in our Genetics Laboratory. Eighty-four (79.2%) patients had the Philadelphia (Ph) chromosome as the sole chromosomal anomaly. Only 49(58.3%) of these 84 patients had sufficient marrow or leukemia blood materials to additionally be included in the array-CGH analysis. Fluorescence in situ hybridization (FISH) was carried out to confirm the genes covered by the deleted or duplicated regions of the CNVs.Results11(22.4%) out of the 49 patients were found to have one to three somatic segmental somatic segmental (CNVs), including fourteen deletions and three duplications. The common region associated with deletions was on 9q33.3-34.12. Identified in five (45.5%) of the 11 positive patients with segmental CNVs, the deletions ranged from 106 kb to 4.1 Mb in size. Two (18.2%) cases had a deletion in the ABL1-BCR fusion gene on der (9), while three (27.3%) cases had a deletion in the ASS1 gene. The remaining CNVs were randomly distributed on different autosomes.ConclusionSubtle genomic CNVs are relatively common in CML patients without cytogenetically visible additional chromosomal aberrations (ACAs). Long-term studies investigating the potential impact on patient prognosis and treatment outcome is underway.

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Section: Discussionmentioning

confidence: 99%

Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update

Zhang

Wang

et al. 2021

Front. Genet.

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“…Genome-wide SNP array analysis was performed using the Affymetrix CytoScan HD platform with approximately 2.7 million probes according to the manufacturer's protocols (Affymetrix, Santa Clara, CA) as published previously. 15 SNP array data were analyzed by the Affymetrix ChAS software version 2.1 (Affymetrix). Plots of two parameters, the log 2 ratio and the allele peaks, providing information regarding copy number and genotype, respectively, were examined by visual inspection.…”

Section: Snp Array Analysismentioning

confidence: 99%

Genome-Wide Single-Nucleotide Polymorphism Array Analysis Improves Prognostication of Acute Lymphoblastic Leukemia/Lymphoma

Wang

Miller

Roulston

et al. 2016

The Journal of Molecular Diagnostics

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Chromosomal abnormalities are important for the risk stratification of acute lymphoblastic leukemia/lymphoma (ALL). However, approximately 30% of pediatric and 50% of adult patients lack abnormalities with clinical relevance by traditional cytogenetic analysis. We integrated cytogenetic, fluorescence in situ hybridization, and whole-genome single-nucleotide polymorphism array results from 60 consecutive clinical ALL cases. By cytogenetic and/or fluorescence in situ hybridization analyses, recurring abnormalities with clinical relevance were observed in 33 B-cell ALL (B-ALL), including t(9;22), hyperdiploidy, KMT2A translocation, ETV6-RUNX1, intrachromosomal amplification of chromosome 21, near haploidy or low hypodiploidy, and t(8;22). Single-nucleotide polymorphism array analysis found additional aberrations with prognostic or therapeutic implication in 21 B-ALL and two T-cell ALL, including IKZF1 deletion, intrachromosomal amplification of chromosome 21 (one case with a normal karyotype), low hypodiploidy (two cases with a normal karyotype), and one case each with fusion genes ETV6-NTRK3, CRLF2-P2RY8, NUP214-ABL1, and SET-NUP214. IKZF1 deletion was noted in nine B-ALL with t(9;22), one B-ALL with t(4;11), five B-ALL with a normal karyotype, and three B-ALL with nonrecurring karyotypic abnormalities. Combining single-nucleotide polymorphism array with chromosome and fluorescence in situ hybridization assays, the detection rate for clinically significant abnormal results increased from 56% to 75%. Whole-genome single-nucleotide polymorphism array analysis detects cytogenetically undetectable clinically significant aberrations and should be routinely applied at diagnosis of ALL.

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“…With respect to cancer treatment, FISH not only identifies genetic or chromosomal anomalies that drive carcinogenesis and tumor progression but also identifies those abnormalities that result in the (over-)production of (potential) therapeutic targets. Examples are (i) the gene fusion product BCR/ABL1 (i.e., the Philadelphia chromosome), which is generated by a t(9;22)(q34.1;q11.2) translocation and frequently found in chronic myeloid leukemias (Shao et al, 2015;Virgili & Nacheva, 2010), and (ii) the HER2/ErbB2 receptor tyrosine kinase gene, which is amplified in ∼20% of all breast (Slamon et al, 2001) and gastric (He et al, 2013) cancers. Thus, patients who are eligible for targetspecific treatments can be identified by cytogenetic analyses.…”

Section: Introductionmentioning

confidence: 99%

Complementary Tumor Diagnosis by Single Cell–Based Cytogenetics Using Multi‐marker Fluorescence In Situ Hybridization (mFISH)

Brockhoff

2023

Current Protocols

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Multi‐color (or multi‐marker) fluorescence in situ hybridization (mFISH) is a well‐established, valuable, complementary tool for prenatal and pathological (tumor) diagnosis. A variety of chromosomal abnormalities, such as partial or total chromosomal gains, losses, inversions, or translocations, which are considered to cause genetic syndromes, can relatively easily be detected on a cell‐by‐cell basis. Individual cells either in suspension (e.g., in the form of a cytological specimen derived from body fluids) or within a tissue (e.g., a solid tumor specimen or biopsy) can be quantitatively evaluated with respect to the chromosomal hybridization markers of interest (e.g., a gene or centromeric region) and with due consideration of cellular heterogeneity. FISH is helpful or even essential for the (sub‐)classification, stratification, and unambiguous diagnosis of a number of malignant diseases and contributes to treatment decision in many cases. Here, the diagnostic power and limitations of typical FISH and mFISH approaches (except chromosome painting and RNA hybridization) are discussed, with special emphasis on tumor and single‐cell diagnostics. Well‐established and novel FISH protocols, the latter addressed to accelerate and flexibilize the preparation and hybridization of formalin‐fixed and paraffin‐embedded tissues, are provided. Moreover, guidelines and molecular aspects important for data interpretation are discussed. Finally, sophisticated multiplexed approaches and those that analyze very rare single‐cell events, which are not yet implemented in diagnostic procedures, will be touched upon. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.This article was corrected on 21 December 2023. See the end of the full text for details.Basic Protocol 1: (m)FISH applied to formaldehyde‐fixed paraffin‐embedded tissuesBasic Protocol 2: (m)FISH applied to cytological specimens

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Cytogenetic, fluorescence in situ hybridization, and genomic array characterization of chronic myeloid leukemia with cryptic BCR-ABL1 fusions

Cited by 7 publications

References 23 publications

Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update

Genomic Copy Number Variants in CML Patients With the Philadelphia Chromosome (Ph+): An Update

Genome-Wide Single-Nucleotide Polymorphism Array Analysis Improves Prognostication of Acute Lymphoblastic Leukemia/Lymphoma

Complementary Tumor Diagnosis by Single Cell–Based Cytogenetics Using Multi‐marker Fluorescence In Situ Hybridization (mFISH)

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