Microarray, gene sequencing, and reverse transcriptase-polymerase chain reaction analyses of a cryptic PML-RARA translocation.

Abstract

Acute promyelocytic leukemia (APL) is a well-defined subtype of acute myeloid leukemia (AML) specifically characterized by the t(15;17)(q22;q12) translocation. The t(15;17) results in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARA) genes. Rare cryptic fusions often associated with small genomic insertions can best be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) although conventional chromosomal studies or even fluorescence in situ hybridization (FISH) analyses appear normal. We report here an APL clone with a cryptic PML-RARA fusion that returned negative results by both karyotyping and fluorescence in situ hybridization (FISH), but returned positive results by RT-PCR analysis. A single nucleotide polymorphism (SNP) microarray analysis was used in this case to help resolve the discordance, revealing a 49-kilobase intragenic PML gene duplication. A dual color dual fusion PML-RARA FISH probe set identified a small, extra PML signal in a chromosome other than 15 or 17. Although coinsertion of a RARA sequence could be detected by neither FISH nor array, the RT-PCR positivity is consistent with this fusion "ectopic" to the natural gene loci. The findings highlight the clinical utility of microarray in cases of cryptic PML-RARA fusion.

• Authors: Jason Koshy, You-Wen Qian, Gayathri Bhagwath, Maurice Willis, Todd W Kelley, Peter Papenhausen
• Journal: Cancer genetics (Cancer Genet) Vol. 205 Issue 10 Pg. 537-40 (Oct 2012) ISSN: 2210-7762 [Print] United States
• PMID: 22982005 (Publication Type: Case Reports, Journal Article)
• Copyright: Published by Elsevier Inc.

Chemical References

• Nuclear Proteins
• Promyelocytic Leukemia Protein
• RARA protein, human
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• Transcription Factors
• Tumor Suppressor Proteins
• PML protein, human

Topics

• Adult
• Chromosome Mapping
• Chromosomes, Human, Pair 15
• Chromosomes, Human, Pair 17
• Gene Dosage
• Gene Duplication
• Humans
• In Situ Hybridization, Fluorescence
• Karyotyping
• Loss of Heterozygosity
• Male
• Nuclear Proteins (genetics)
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide
• Promyelocytic Leukemia Protein
• RNA Splicing
• Receptors, Retinoic Acid (genetics)
• Retinoic Acid Receptor alpha
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Sequence Analysis, DNA
• Transcription Factors (genetics)
• Translocation, Genetic
• Tumor Suppressor Proteins (genetics)