Identification of clinically important chromosomal aberrations in acute myeloid leukemia by array-based comparative genomic hybridization

Abstract

Array-based comparative genomic hybridization (aCGH) chromosomal analysis facilitates rapid detection of cytogenetic abnormalities previously undetectable by conventional cytogenetics. In this study, we analyze 48 uniformly treated acute myeloid leukemia (AML) patients by 44K aCGH and correlated the findings with clinical outcome. aCGH identified previously undetected aberrations, as small as 5 kb, of currently unknown significance. The 36.7 Mb minimally deleted region on chromosome 5 lies between 5q14.3 to 5q33.3 contains 634 genes and 15 microRNAs whereas loss of chromosome 17 spans 3,194 kb involves 342 genes and 12 microRNAs. Loss of 155 kilobase (kb) region on 5q33.3 (p<0.05) is associated with achievement of complete remission. In contrast, loss of 17p11.2-q11.1 was associated with lower CR rate and poorer overall survival (Kaplan-Meier analysis, p<0.0096). aCGH detected loss of 17p in 12/48 patients as compared to 9/48 by conventional karyotyping. In conclusion, aCGH analysis adds to the prognostic stratification of AML patients.

Application of Molecular Karyotyping in Acute Myeloid Leukemia: A Review

“…Our analysis also revealed high burden of CNVs in our cases, which contradict previous reports [35] [53]. However, these findings significantly support reports by Mehrotra et al and Jun et al whereby the studies observed more than two-fold of CNVs in their samples [48] [50]. Studies by Mehrotra et al and Jun et al, however, lacked systematic use of germline DNA and thus, there could be overestimation of somatic CNVs.…”

“…In another study by Mehrotra et al, 48 AML uniformly treated AML patients were tested with a custom-designed 4X44K, 60-mer oligonucleotide genomic array with genecentric whole genome coverage [50]. Mehrotra's research group detected a total of 170 CNVs and reported that frequencies of sub-microscopic aberrations were higher compared to whole chromosomal abnormalities.…”

Double inv(3)(q21q26.2) in acute myeloid leukemia is resulted from an acquired copy neutral loss of heterozygosity of chromosome 3q and associated with disease progression

“…Genomic DNA was extracted from bone marrow aspirate material using Gentra Puregene (Qiagen, Valencia, CA). The Cancer Cytogenomic Microarray Consortium (CCMC) 4x180K chip was used according to the manufacturer’s protocol (Agilent Technologies, Santa Clara, CA) as described previously [ 25 ]. The Agilent GeneChip microarray scanner was used for imaging and data analysis was performed using Cytogenomic workbench software.…”

Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group

“…Of note, due to poor morphology and complexity of chromosomal abnormalities, such deletions may remain cryptic by karyotype analysis. In one study involving AML with a complex karyotype, CMA testing identified 17p deletions encompassing TP53 in 6% of additional cases in which they were not detected by conventional karyotype analysis [88].…”