Jumping translocations in hematological malignancies: a cytogenetic study of five cases

Laboratory of Cytogenetics, NCSR "Demokritos" Athens, Greece.
Cancer genetics and cytogenetics (Impact Factor: 1.93). 01/2009; 187(2):85-94. DOI: 10.1016/j.cancergencyto.2008.07.010
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Jumping translocations (JT) are rare cytogenetic aberrations in hematological malignancies that include unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to two or more different recipient chromosomes in different cell lines. We report five cases associated with different hematologic disorders and JT to contribute to the investigation of the origin, pathogenesis, and clinical significance of JT. These cases involve JT of 1q in a case of acute myeloblastic leukemia (AML)-M1, a case of Burkitt lymphoma, and a case of BCR/ABL-positive acute lymphoblastic leukemia, as well as a JT of 13q in a case of AML-M5, and a JT of 11q segment in a case of undifferentiated leukemia. To our knowledge, with regard to hematologic malignancies, this study presents the first case of JT associated with AML-M1, the first case of JT involving 13q as a donor chromosome, and the first report of JT involving a segment of 11q containing two copies of the MLL gene, jumping on to two recipient chromosomes in each cell line and resulting in six copies of the MLL gene. Our investigation suggests that JT may not contribute to the pathogenesis but rather to the progression of the disease, and it demonstrates that chromosome band 1q10 as a breakpoint of the donor chromosome 1q is also implicated in AML, not only in multiple myeloma as it has been known until now.

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Available from: Vasileios N. Georgakakos, Oct 07, 2015
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    • "It is seen in all ages and appears to be associated with a dismal prognosis (3,4). Nevertheless, survivals longer than 36 months have been reported in 3 childhood cases one of which was an ALL (4–6). The same fusion FUS/ERG has also been found in 3 Ewing tumors (8,9); it is thus one of the relatively few fusion genes that exert pathogenetic influence in widely disparate neoplastic entities. "
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    ABSTRACT: Sequential combination of cytogenetics and RNA-sequencing (RNA-Seq) has been shown to be an efficient approach to detect pathogenetically important fusion genes in neoplasms carrying only one or a few chromosomal rearrangements. We performed RNA-Seq on an acute myeloid leukemia in a 2-year-old girl with the karyotype 46,XX,add(1)(p36), der(2)t(2;3)(q21;q21),del(3)(q21),der(10)t(1;10)(q32;q24),der(16)(2qter-->2q21::16p11-->16q24::16p11-->16pter)[13]/46,XX[2] and identified a cryptic FUS/ERG fusion gene. PCR and direct sequencing verified the presence of the FUS-ERG chimeric transcript in which exon 7 of FUS from 16p11 (nt 904 in sequence with accession number NM_004960 version 3) was fused in frame to exon 8 of ERG from sub-band 21q22.2 (nt 967 in NM_004449 version 4). The FUS-ERG transcript found here has been reported in only two other cases of childhood leukemia, in a 1-year-old boy and an 8-month-old boy, both diagnosed with precursor B cell ALL. The fusion transcript codes for a 497 amino acid residues FUS-ERG protein and, similar to other AML-related FUS-ERG fusion proteins, contains both functional domains (TR1 and TR2) of the transactivation domain of FUS and the ETS domain of ERG. The clinical significance, if any, of the amino acid residues which are coded by the exons 8, 9 and 10 of ERG in the fusion FUS-ERG proteins, remains unclear.
    Oncology Reports 09/2013; 30(6). DOI:10.3892/or.2013.2751 · 2.30 Impact Factor
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    • "A detailed review of these abnormalities was recently published (Berger & Bernard, 2007). The occurrence of JT and, specifically, amplification of the long arms of chromosome 1 (1qJT) is an independent indicator of poor outcome in multiple myeloma patients (Sawyer et al, 2005; Hanamura et al, 2006) but due to their rarity in myeloid malignancies (Najfeld et al, 1995; Djordjevic et al, 2008; Manola et al, 2008) it is uncertain whether this abnormality contributes to disease progression. We retrospectively investigated 1qJT in 23 patients with myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS) who were evaluated in the Tumor Cytogenetics Laboratory at the Mount Sinai School of Medicine between 1984 and 2009. "
    British Journal of Haematology 11/2010; 151(3):288-91. DOI:10.1111/j.1365-2141.2010.08355.x · 4.71 Impact Factor
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    ABSTRACT: Reciprocal t(16;21)(p11;q22) is a rare chromosomal abnormality in acute myeloid leukemia (AML). The chimeric transcript FUS-ERG formed by this translocation which causes the replacement of RNA-binding domain of FUS (alias TLS) with the DNA-binding domain of ERG, and this event is thought to be responsible for leukemogenesis. Here we report two cases of AML with t(16;21)(p11.2;q22) showing unusual characteristics, and address the clinical, hematological, and molecular aspects of leukemia with t(16;21), along with a review of the literature.
    Cancer genetics and cytogenetics 10/2009; 194(2):111-8. DOI:10.1016/j.cancergencyto.2009.06.010 · 1.93 Impact Factor
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