Interpretation of submicroscopic deletions of the BCR or ABL gene should not depend on extra signal-FISH: Problems in interpretation of submicroscopic deletion of the BCR or ABL gene with extra signal-FISH

Young Ree Kim, Han Ik Cho, Sung Soo Yoon, Seonyang Park, Byoung Kook Kim, Young Kyung Lee, Honggu Chun, Hee Chan Kim, Dong Soon Lee

Research output: Contribution to journalArticle

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Abstract

Several groups have demonstrated that a submicroscopic gene deletion in Ph+ chronic myelogenous leukemia (CML) is associated with a poor prognosis and reduced response to treatment. To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion, we performed an extra signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative myeloproliferative disorder as determined by RT-PCR. The normal cutoff values were 0.22% for ES-FISH and 0.25% for D-FISH. The cutoff values for false-positive signals from a juxtaposition of the BCR and ABL gene were 11% in ES-FISH and 13% in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the 79 patients (15.8%), and the main causes of a discrepancy were a false-positive ABL deletion (4 of 12, 33%), a variant Philadelphia chromosome (3 of 12, 25%), an inversion of derivative chromosome 9 at the very breakpoint of the ABL gene (9q32) (1 of 12, 8.3%), a cryptic variant Ph chromosome (1 of 12, 8.3%), and a marker chromosome (1 of 12, 8.3%). Although there was no significant difference in the sensitivity for the detection of the fusion signal between ES- and D-FISH, ES-FISH showed a high percentage of cells with false-positive fusion signals (1 orange, 1 green, 1 yellow), which makes it difficult to interpret the submicroscopic ABL deletion. In conclusion, an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalGenes Chromosomes and Cancer
Volume43
Issue number1
DOIs
Publication statusPublished - 2005 May 1
Externally publishedYes

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Chromosomes, Human, Pair 12
Gene Deletion
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Genes
Blast Crisis
Philadelphia Chromosome
Myeloproliferative Disorders
Chromosomes, Human, Pair 9
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 1
Bone Marrow Cells
Reference Values
Polymerase Chain Reaction
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Interpretation of submicroscopic deletions of the BCR or ABL gene should not depend on extra signal-FISH : Problems in interpretation of submicroscopic deletion of the BCR or ABL gene with extra signal-FISH. / Kim, Young Ree; Cho, Han Ik; Yoon, Sung Soo; Park, Seonyang; Kim, Byoung Kook; Lee, Young Kyung; Chun, Honggu; Kim, Hee Chan; Lee, Dong Soon.

In: Genes Chromosomes and Cancer, Vol. 43, No. 1, 01.05.2005, p. 37-44.

Research output: Contribution to journalArticle

Kim, Young Ree ; Cho, Han Ik ; Yoon, Sung Soo ; Park, Seonyang ; Kim, Byoung Kook ; Lee, Young Kyung ; Chun, Honggu ; Kim, Hee Chan ; Lee, Dong Soon. / Interpretation of submicroscopic deletions of the BCR or ABL gene should not depend on extra signal-FISH : Problems in interpretation of submicroscopic deletion of the BCR or ABL gene with extra signal-FISH. In: Genes Chromosomes and Cancer. 2005 ; Vol. 43, No. 1. pp. 37-44.
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abstract = "Several groups have demonstrated that a submicroscopic gene deletion in Ph+ chronic myelogenous leukemia (CML) is associated with a poor prognosis and reduced response to treatment. To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion, we performed an extra signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative myeloproliferative disorder as determined by RT-PCR. The normal cutoff values were 0.22{\%} for ES-FISH and 0.25{\%} for D-FISH. The cutoff values for false-positive signals from a juxtaposition of the BCR and ABL gene were 11{\%} in ES-FISH and 13{\%} in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the 79 patients (15.8{\%}), and the main causes of a discrepancy were a false-positive ABL deletion (4 of 12, 33{\%}), a variant Philadelphia chromosome (3 of 12, 25{\%}), an inversion of derivative chromosome 9 at the very breakpoint of the ABL gene (9q32) (1 of 12, 8.3{\%}), a cryptic variant Ph chromosome (1 of 12, 8.3{\%}), and a marker chromosome (1 of 12, 8.3{\%}). Although there was no significant difference in the sensitivity for the detection of the fusion signal between ES- and D-FISH, ES-FISH showed a high percentage of cells with false-positive fusion signals (1 orange, 1 green, 1 yellow), which makes it difficult to interpret the submicroscopic ABL deletion. In conclusion, an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.",
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AU - Kim, Young Ree

AU - Cho, Han Ik

AU - Yoon, Sung Soo

AU - Park, Seonyang

AU - Kim, Byoung Kook

AU - Lee, Young Kyung

AU - Chun, Honggu

AU - Kim, Hee Chan

AU - Lee, Dong Soon

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N2 - Several groups have demonstrated that a submicroscopic gene deletion in Ph+ chronic myelogenous leukemia (CML) is associated with a poor prognosis and reduced response to treatment. To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion, we performed an extra signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative myeloproliferative disorder as determined by RT-PCR. The normal cutoff values were 0.22% for ES-FISH and 0.25% for D-FISH. The cutoff values for false-positive signals from a juxtaposition of the BCR and ABL gene were 11% in ES-FISH and 13% in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the 79 patients (15.8%), and the main causes of a discrepancy were a false-positive ABL deletion (4 of 12, 33%), a variant Philadelphia chromosome (3 of 12, 25%), an inversion of derivative chromosome 9 at the very breakpoint of the ABL gene (9q32) (1 of 12, 8.3%), a cryptic variant Ph chromosome (1 of 12, 8.3%), and a marker chromosome (1 of 12, 8.3%). Although there was no significant difference in the sensitivity for the detection of the fusion signal between ES- and D-FISH, ES-FISH showed a high percentage of cells with false-positive fusion signals (1 orange, 1 green, 1 yellow), which makes it difficult to interpret the submicroscopic ABL deletion. In conclusion, an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.

AB - Several groups have demonstrated that a submicroscopic gene deletion in Ph+ chronic myelogenous leukemia (CML) is associated with a poor prognosis and reduced response to treatment. To assess the variation between detection methods in the interpretation of a submicroscopic gene deletion, we performed an extra signal (ES)-FISH BCR/ABL and double-FISH (D-FISH) BCR/ABL on frozen bone marrow cells from 79 patients with CML (63 in the chronic phase, 6 in the accelerated phase, and 10 in blast crisis) and 30 patients with a BCR/ABL-negative myeloproliferative disorder as determined by RT-PCR. The normal cutoff values were 0.22% for ES-FISH and 0.25% for D-FISH. The cutoff values for false-positive signals from a juxtaposition of the BCR and ABL gene were 11% in ES-FISH and 13% in D-FISH. Of the 14 patients who showed an ABL gene deletion by ES-FISH, 5 had an ABL deletion only, 5 had both a BCR and an ABL deletion, but 4 proved to have a classic BCR/ABL rearrangement without a submicroscopic deletion, as determined by D-FISH. Discrepant results between ES- and D-FISH were observed in 12 of the 79 patients (15.8%), and the main causes of a discrepancy were a false-positive ABL deletion (4 of 12, 33%), a variant Philadelphia chromosome (3 of 12, 25%), an inversion of derivative chromosome 9 at the very breakpoint of the ABL gene (9q32) (1 of 12, 8.3%), a cryptic variant Ph chromosome (1 of 12, 8.3%), and a marker chromosome (1 of 12, 8.3%). Although there was no significant difference in the sensitivity for the detection of the fusion signal between ES- and D-FISH, ES-FISH showed a high percentage of cells with false-positive fusion signals (1 orange, 1 green, 1 yellow), which makes it difficult to interpret the submicroscopic ABL deletion. In conclusion, an interpretation of the submicroscopic deletions of the BCR or ABL gene should not depend on ES-FISH.

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