Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes

Kolquist, Kathryn A.; Schultz, Roger A.; Furrow, Aubry; Brown, Theresa C.; Han, Jin Yeong; Campbell, Lynda J.; Wall, Meaghan; Slovak, Marilyn L.; Shaffer, Lisa G.; Ballif, Blake C.

doi:10.1016/j.cancergen.2011.10.004

Cited by 57 publications

(50 citation statements)

References 48 publications

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“…Anyway, it can be assumed that at least 5% of MDS/AML have ETV6 deletion [15,16]. This frequency has been shown to be much higher in association with monosomy 7 [12,17,18]. Wall et al tested ETV6 deletion in a series of 38 patients with diagnosis of MDS/MPN (myeloproliferative neoplasms) or AML with monosomy 7 [19].…”

Section: Discussionmentioning

confidence: 99%

A 14.8 Mb 12p Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome

Valetto¹,

Bertini²,

Ciabatti³

et al. 2017

HGCR

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We present on a new case of myelodysplastic syndrome characterized by array Comparative Genomic Hybridization. This technique confirmed the monosomy 7, detected by conventional cytogenetics, and revealed also a deletion on the short arm of chromosome 12. This deletion extends for about 14.8 Mb and breaks ETV6 gene.12p deletion extents in hematological malignancies may vary, but the minimally deleted region almost invariably contains ETV6, that is considered the main candidate tumor suppressor genes within the region for tumor progression. It has been shown that levels of ETV6 were significantly decreased in cases with 12p13 deletions, whereas expression of other genes in the deleted region, like BCL2L14, LRP6, DUSP16 and GPRC5D, did not show any variation, independently of their copy number status. This observation strengthens the fact that ETV6 may play a potential role in the tumorigenesis process. The role of ETV6 in our patient myelodysplastic syndrome is showed by his clinical history and his poor prognosis.

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Section: Discussionmentioning

confidence: 99%

A 14.8 Mb 12p Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome

Valetto¹,

Bertini²,

Ciabatti³

et al. 2017

HGCR

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“…Labeling, hybridization, and washing were performed using previously published methods [21]. Data were analyzed and displayed using custom oligonucleotide aCGH data analysis and visualization software (Oncoglyphix ® ; Signature Genomics) as previously described [22]. Variants were identified based on the number of consecutive oligonucleotides involved and the magnitude in shift for the log2 ratio, with 5 -99 oligonucleotides requiring a shift ≥ 0.300, 100 -999 a shift ≥ 0.200, and a ≥ 1000 a shift ≥ 0.100.…”

Section: Oligonucleotide Microarray Labeling Hybridization and Analysismentioning

confidence: 99%

CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all

Schultz¹,

Tsuchiya²,

Furrow³

et al. 2013

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Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with the majority of cases being of precursor B-cell phenoltype. Conventional cytogenetic analysis plays an important role in the diagnosis of B-cell ALL, identifying characteristic chromosomal abnormalities associated with a given prognosis therein facilitating optimized treatment. The more recent introduction of microarray technology to the analysis of B-cell ALL has afforded both higher resolution for the detection of known abnormalities and an ability to identify novel copy number abnormalities (CNAs) with potential clinical relevance. In the current study, microarray analysis was performed on 20 cytogenetically abnormal B-cell ALL cases (10 pediatric and 10 adult), while a novel microarray-based balancedtranslocation detection methodology (translocation CGH or tCGH) was applied to that subset of cases with a known or suspected recurrent balanced translocation. Standard microarray analysis identified that CNAs was not detected by previous conventional cytogenetics in 75% (15/20) cases. tCGH identified 9/9 (100%) balanced translocations defining BCR/ABL1 (x4), ETV6/RUNX1 (x3), and MLL/AFF1 (x2) breakpoints with high resolution. The results illustrate the improved molecular detail afforded by these technologies and a comparison of translocation breakpoints, CNAs and patient age offers new insights into tumor biology with potential prognostic significance.

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“…The standard resolution varies between 1-5 Mb and can be increased up to approximately 40 kb. Part of the aCGH procedure is semi-automated and results are analysed using a biostatistical algorithm 32,33 . A number of different array-based approaches have been developed, aiming to improve resolution of aCGH in particular 34 .…”

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confidence: 99%

“…A number of different array-based approaches have been developed, aiming to improve resolution of aCGH in particular 34 . Currently, there are commercially available array-based DNA platforms (bacterial artificial chromosome -BAC, oligonucleotide, single-nucleotide polymorphism -SNP), synonymous names being chromosomal microarray or molecular karyotyping 31,32 . The genomic resolution of the different aCGH platforms is determined by spacing and length of the DNA probes (e.g.…”

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confidence: 99%

“…In oncohematology, microarrays can be used to refine diagnosis, identify novel disease subtypes, predict response to treatment and identify genes and pathways linked to pathogenesis, thus defining targets to rational therapy 37 . Slovak et al 32 revealed, using a genome-wide BAC-based 41 . MDS offers a compelling model for SNP array investigation to uncover novel clonal molecular changes with implications for pathogenesis, evaluation of their effects on disease progression and response to treatment 40 .…”

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confidence: 99%

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Molecular genetic methods in the diagnosis of myelodysplastic syndromes. A review

Lukackova¹,

Bujalkova²,

Majerova³

et al. 2014

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Myelodysplastic syndromes (MDS) represent a heterogeneous group of premalignant hematologic disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias and increased risk of progression to acute leukemia. Cytogenetic analysis still plays a central role in the diagnosis of MDS, as clonal chromosomal abnormalities are observed in 30-50% of MDS patients. Despite their technical limitations, standard karyotyping and fluorescence in situ hybridization (FISH) are routinely used for identifying recurrent chromosomal rearrangements. However, using this approach means that submicroscopic and not targeted chromosomal aberrations, as well as somatic mutations and epigenetic changes remain largely undetected. Methods and Results. Introduction of methods for the analysis of copy-number variations (CNV), including arraybased technologies and Multiplex ligation-dependent probe amplification (MLPA) has provided novel insights into the molecular pathogenesis of MDS and considerably extended possibilities for genetic laboratory testing. Several novel molecular markers have been discovered and used for diagnosis and prognostic evaluation of patients with MDS. At present, mutational analysis is not routinely performed, as the clinical significance of somatic mutations in MDS has only begun to emerge. However, recently introduced Next-generation sequencing (NGS) technologies could help to elucidate the relationship between chromosomal and molecular aberrations in MDS and lead to further improvement in its diagnosis. Conclusion. This review focuses on the advantages, limitations, clinical applications and future perspectives of three molecular methods (array-based analysis, MLPA and NGS) currently used in genetic testing and/ or translational research of MDS. In conclusion, a brief summary for clinicians from the routine diagnostic point of view is given.

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Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes

Cited by 57 publications

References 48 publications

A 14.8 Mb 12p Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome

A 14.8 Mb 12p Deletion Disrupting ETV6 in a Patient with Myelodysplastic Syndrome

CGH-based microarray detection of cryptic and novel copy number alterations and balanced translocations in cytogenetically abnormal cases of b-cell all

Molecular genetic methods in the diagnosis of myelodysplastic syndromes. A review

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