Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia.

Authors

Renu Bajaj, Cytogenetics Laboratory, Departments of Pathology, Anatomy and Cell Biology, Thomas Jefferson University Hospital; Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of MedicineFollow
Fang Xu, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine
Bixia Xiang, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine; Department of Cytogenetics, City of Hope, Duarte, CA
Katherine Wilcox, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine
Autumn J Diadamo, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine
Rachana Kumar, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine
Alexandra Pietraszkiewicz, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine
Stephanie Halene, Section of Hematology, Department of Internal Medicine, Yale University School of Medicine
Peining Li, Molecular Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine

Document Type

Article

Publication Date

1-20-2011

Comments

This article has been peer reviewed and is published in Molecular Cytogenetics 2011, 4:3. The published version is available at DOI: 10.1186/1755-8166-4-3. ©BioMed Central Ltd.

Abstract

BACKGROUND: To evaluate the clinical validity of genome-wide oligonucleotide array comparative genomic hybridization (aCGH) for detecting somatic abnormalities, we have applied this genomic analysis to 30 cases (13 MDS and 17 AML) with clonal chromosomal abnormalities detected in more than 50% of analyzed metaphase cells.

RESULTS: The aCGH detected all numerical chromosomal gains and losses from the mainline clones and 113 copy number alterations (CNAs) ranging from 0.257 to 102.519 megabases (Mb). Clinically significant recurrent deletions of 5q (involving the RPS14 gene), 12p12.3 (ETV6 gene), 17p13 (TP53 gene), 17q11.2 (NF1 gene) and 20q, double minutes containing the MYC gene and segmental amplification involving the MLL gene were further characterized with defined breakpoints and gene contents. Genomic features of microdeletions at 17q11.2 were confirmed by FISH using targeted BAC clones. The aCGH also defined break points in a derivative chromosome 6, der(6)t(3;6)(q21.3;p22.2), and an isodicentric X chromosome. However, chromosomally observed sideline clonal abnormalities in five cases were not detected by aCGH.

CONCLUSIONS: Our data indicated that an integrated cytogenomic analysis will be a better diagnostic scheme to delineate genomic contents of chromosomal and cryptic abnormalities in patients with MDS and AML. An evidence-based approach to interpret somatic genomic findings was proposed.

Recommended Citation

Bajaj, Renu; Xu, Fang; Xiang, Bixia; Wilcox, Katherine; Diadamo, Autumn J; Kumar, Rachana; Pietraszkiewicz, Alexandra; Halene, Stephanie; and Li, Peining, "Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia." (2011). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 73.
https://jdc.jefferson.edu/pacbfp/73

PubMed ID

21251322