Cancer Genetics and Cytogenetics 157 (2005) 74–77
Short communication
Molecular and cytogenetic characterization of a novel
rearrangement involving chromosomes 9, 12, and 17
resulting in ETV6 (TEL) and ABL fusion
C.A. Tirado
a,1,
*
, S. Sebastian
a,1
, J.O. Moore
b
, J.Z. Gong
a
, B.K. Goodman
a
a
Department of Pathology, Duke University Medical Center, Box 3631, M347 Davison Bldg., Durham, NC 27710
b
Division of Hematology-Oncology, Duke University Medical Center, Durham, NC
Received 2 March 2004; received in revised form 26 May 2004; accepted 3 June 2004
Abstract
We performed chromosome analysis on the bone marrow of a patient with BCR/ABL negative
chronic myelogenous leukemia (CML). By interphase fluorescence in situ hybridization (FISH), an
extra ABL signal was present in interphase nuclei and appeared to be located at 17p in the
metaphase cells. Chromosome analysis showed a subtle abnormality at 17p13 and 12p13 but no visible
rearrangement at 9q34 (ABL). Additional FISH experiments disclosed a rearrangement between
the short arms of chromosomes 12 and 17 at approximately bands 12p13 and 17p13, respectively.
In addition, subtelomeric FISH analysis confirmed the presence of terminal 12p at 17p13 and
showed terminal 9q34 to be intact on each chromosome 9. Taken together, these results indicated
a rearrangement involving chromosomes 9, 12, and 17 that suggested the possibility of juxtaposition
of part of the ETV6 (also known as TEL) locus (12p13) with a portion of ABL (9q34) together at
17p13. The ETV6/ABL fusion was confirmed by RT-PCR, which showed that the first 5 exons of
ETV6 were fused in frame with ABL at exon 2. Wild-type ETV6 and ABL were also expressed, in
accordance with the FISH results that showed no loss of the second ETV6 or ABL allele.
Ć
2005
Elsevier Inc. All rights reserved.
1. Introduction
Chronic myeloid leukemia (CML) is a chronic myelo-
proliferative disorder characterized by the Philadelphia
chromosome t(9;22) involving the BCR/ABL gene fusion
with a constitutive tyrosine kinase activity. There is a second
group of CML patients that have a cryptic translocation
between BCR and ABL or show a complex translocation
involving a third chromosome. We report here the identifica-
tion of a novel rearrangement in a CML patient involving
chromosomes 9, 12, and 17 resulting in ETV6(TEL) and
ABL fusion. To our knowledge, the involvement of an ETV/
ABL fusion together in a complex three-way rearrangement
with a locus on the short arm of chromosome 17 has not been
reported previously. This patient appears to be responding
favorably to imantib mesylate (Gleevec; Novartis Pharma-
ceuticals, East Hanover, NJ) therapy.
1
These authors contributed equally to this manuscript.
* Corresponding author. Tel.: (703) 802-8900 x5328; fax: (703) 802-
7103.
E-mail address: carlos.a.tirado@questdiagnostics.com (C.A. Tirado).
0165-4608/05/$ – see front matter
Ć
2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.cancergencyto.2004.06.001
2. Clinical presentation
A 72-year-old man presented with thrombocytopenia
(platelet count of 32 × 10
3
/µL) and a history of negative
BCR/ABL fusion by RT-PCR. Over the past year, he
presented with intermittent abdominal pain, nausea, and oc-
casional diarrhea. His hemoglobin was 9.8 g/dL. His white
blood cell count was 5.7 × 10
9
/µL with 5% blasts. Flow
cytometry studies of bone marrow showed 45% blasts, which
were positive for B-cell antigens CD10, CD19, CD20, and
CD22. The blasts also aberrantly expressed the myeloid asso-
ciated antigen CD33. Morphologic examination of bone
marrow suggested CML with B-lymphoblastic leukemia
transformation.
3. Materials and methods
3.1. Cytogenetics
Bone marrow was cultured in RPMI 1640 and Chang
BMC media (both from Irvine Scientific, Santa Ana, CA)
and harvested using standard cytogenetic techniques. Slides