Acute promyelocytic leukemia with insertion of PML exon 7a and partial deletion of exon 3 of RARA

a novel variant transcript related to aggressive course and not detected with real-time polymerase chain reaction analysis

Tae Sung Park, Jinseok Kim, Jaewoo Song, Kyunga Lee, Seoyoung Yoon, Borum Suh, Jong Han Lee, Hyeon Ji Lee, Jong Kee Kim, Jong Rak Choi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinct breakpoint cluster region 2 (bcr2) variant transcript. Findings from bone marrow, cytogenetic, fluorescence in situ hybridization, and qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were consistent with the diagnosis of APL. Although PCR products of size 841 bp and 984 bp were amplified from bone marrow specimen, the quantitative PCR (RQ-PCR) findings were negative. Given the discrepancy in PCR results, sequencing of PCR products was performed to determine the detailed composition of these fusion transcripts. By cloning and sequencing, we discovered that these two bands were isoforms, in which one exon (exon 5, 144 bp) of the PML gene was spliced out of the smaller products (minor PCR products); one sequence (G) insertion and one base substitution (T→C) of PML exon 4 generate a stop codon in the smaller fusion transcript. In addition, a search of the Ensembl database revealed that these variant PML/RARA fusion transcripts were composed of exon 7a insertion of the PML gene and partial deletion (46 bp) of exon 3 of the RARA gene, in addition to inserted sequences of intron 7 of PML and genomic sequence ATCT of unknown origin at the fusion junction site. Although the biological significance of most atypical transcripts remains unclear, sequence analysis of these atypical products should be performed, to reveal the composition of such a fusion transcript and elucidate the molecular mechanism.

Original languageEnglish
Pages (from-to)103-107
Number of pages5
JournalCancer genetics and cytogenetics
Volume188
Issue number2
DOIs
Publication statusPublished - 2009 Jan 15

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Acute Promyelocytic Leukemia
Real-Time Polymerase Chain Reaction
Exons
Polymerase Chain Reaction
Bone Marrow
Recombinant DNA
Terminator Codon
Insertional Mutagenesis
Gene Deletion
Reverse Transcriptase Polymerase Chain Reaction
Fluorescence In Situ Hybridization
Cytogenetics
Introns
Sequence Analysis
Organism Cloning
Protein Isoforms
Databases
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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title = "Acute promyelocytic leukemia with insertion of PML exon 7a and partial deletion of exon 3 of RARA: a novel variant transcript related to aggressive course and not detected with real-time polymerase chain reaction analysis",
abstract = "We report the case of a 38-year-old man with acute promyelocytic leukemia (APL) showing a distinct breakpoint cluster region 2 (bcr2) variant transcript. Findings from bone marrow, cytogenetic, fluorescence in situ hybridization, and qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were consistent with the diagnosis of APL. Although PCR products of size 841 bp and 984 bp were amplified from bone marrow specimen, the quantitative PCR (RQ-PCR) findings were negative. Given the discrepancy in PCR results, sequencing of PCR products was performed to determine the detailed composition of these fusion transcripts. By cloning and sequencing, we discovered that these two bands were isoforms, in which one exon (exon 5, 144 bp) of the PML gene was spliced out of the smaller products (minor PCR products); one sequence (G) insertion and one base substitution (T→C) of PML exon 4 generate a stop codon in the smaller fusion transcript. In addition, a search of the Ensembl database revealed that these variant PML/RARA fusion transcripts were composed of exon 7a insertion of the PML gene and partial deletion (46 bp) of exon 3 of the RARA gene, in addition to inserted sequences of intron 7 of PML and genomic sequence ATCT of unknown origin at the fusion junction site. Although the biological significance of most atypical transcripts remains unclear, sequence analysis of these atypical products should be performed, to reveal the composition of such a fusion transcript and elucidate the molecular mechanism.",
author = "Park, {Tae Sung} and Jinseok Kim and Jaewoo Song and Kyunga Lee and Seoyoung Yoon and Borum Suh and Lee, {Jong Han} and Lee, {Hyeon Ji} and Kim, {Jong Kee} and Choi, {Jong Rak}",
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Acute promyelocytic leukemia with insertion of PML exon 7a and partial deletion of exon 3 of RARA : a novel variant transcript related to aggressive course and not detected with real-time polymerase chain reaction analysis. / Park, Tae Sung; Kim, Jinseok; Song, Jaewoo; Lee, Kyunga; Yoon, Seoyoung; Suh, Borum; Lee, Jong Han; Lee, Hyeon Ji; Kim, Jong Kee; Choi, Jong Rak.

In: Cancer genetics and cytogenetics, Vol. 188, No. 2, 15.01.2009, p. 103-107.

Research output: Contribution to journalArticle

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T1 - Acute promyelocytic leukemia with insertion of PML exon 7a and partial deletion of exon 3 of RARA

T2 - a novel variant transcript related to aggressive course and not detected with real-time polymerase chain reaction analysis

AU - Park, Tae Sung

AU - Kim, Jinseok

AU - Song, Jaewoo

AU - Lee, Kyunga

AU - Yoon, Seoyoung

AU - Suh, Borum

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AU - Lee, Hyeon Ji

AU - Kim, Jong Kee

AU - Choi, Jong Rak

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