Short communicationA common 93-kb duplicated DNA sequence at 1q21.2 in acute lymphoblastic leukemia and Burkitt lymphoma
Introduction
Chromosome 1 long arm duplications, or dup(1q), and trisomy 1q are recurrent changes in chronic myeloproliferative disorders, multiple myeloma (MM), acute lymphoblastic leukemia (ALL), and Burkitt lymphoma/leukemia (BL).
In chronic myeloproliferative disorders, both a 1q23∼q32 duplication and an unbalanced 1q translocation with various chromosomes, producing a gain of the entire 1q arm, have been observed [1]. In up to 40% of patients with MM, 1q12∼q32 duplications, whole-arm translocations, or jumping translocations are associated with complex karyotypes, aggressive disease, and poor prognosis [2]. In BL, dup(1q) is the most frequent secondary change associated with t(8;14)(q24;q32); it appears to be linked to disease progression rather than pathogenesis [3], [4]. Whether dup(1q) and trisomy 1q in lymphoid and myeloid malignancies underlie the same molecular lesions remains to be established.
We characterized dup(1q) in lymphoid malignancies and identified a common 1q21.2 duplicated region in three cases of ALL and one case of BL. Our findings provide the basis for designing molecular studies to investigate any putative oncogenes or tumor suppressor genes that could underlie 1q duplication in ALL and BL.
Section snippets
Patients
We studied three ALL (patients 1–3) and one BL (patient 4) at diagnosis (Table 1). Conventional cytogenetic and fluorescence in situ hybridization (FISH) analyses were performed on bone marrow cells (patients 1–3) and pleural and ascitic effusion (patient 4).
Cytogenetics
Karyotypes were obtained on G-banded metaphases after 24- and 48-hour cultures and were described according to ISCN 2005 [5].
FISH
Metaphase FISH was performed in dual-color experiments, as previously described, with 34 DNA clones for the 1q arm
Patients
Two of the patients were male (1 ALL; 1 BL) and two were female (2 ALL). Two ALL patients and the one BL patient were children (5, 9, and 11 years old) and one ALL patient was a 46-year-old adult. Clinical and hematological features and cytogenetic findings are summarized in Table 1.
Cytogenetics
In patients 1 and 2, dup(1q) was present in hyperdiploid karyotypes. Patient 3 had three leukemic clones. A reciprocal t(1;18)(q21;q12) was common to all. It was isolated in the main clone and associated with
Discussion
The genomic mechanisms and molecular lesions underlying dup(1q) in lymphoid malignancies remain to be established. To date, FISH studies have mapped dup(1q) centromeric breakpoints in the centric or pericentric region of chromosome 1 within, or in close proximity to, the heterochromatic sequences [10]. The present study identified a minimal common duplicated DNA euchromatic sequence in four cases of ALL/BL.
Although 1q duplicons in ALL and BL have various sizes with different proximal and distal
Acknowledgments
AIRC (Associazione Italiana Ricerca sul Cancro), CNR-MIUR (Consiglio Nazionale delle Ricerche-Ministero per l'Istruzione, l'Università e la Ricerca Scientifica); Fondazione Cassa di Risparmio, Perugia, Italy; FIRB, Italy; and Associazione “Sergio Luciani,” Fabriano, Italy. B.C. is supported by a grant from FIRC (Fondazione Italiana Ricerca sul Cancro). BAC clones were kindly provided by Dr. Mariano Rocchi (DAPEG Sez di Genetica, University of Bari, Italy); Telomeric DNA clones were kindly
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DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-κB
2011, Journal of Biological ChemistryCitation Excerpt :Similar to A20, Cezanne has been shown to inhibit NF-κB through modulation of the ubiquitination state of two of its positive regulators, RIP-1 and TRAF6 (21, 22). Cezanne is implicated in cancer biology as a 93-kb sequence containing Cezanne was shown to be duplicated in acute lymphoblastic leukemia and Burkitt lymphoma (23). Although the precise role of Cezanne in cancer is unknown, its inhibition of NF-κB would suggest that Cezanne may act as a tumor suppressor.
Inverted duplication dup(1)(q32q21) as sole aberration in lymphoid and myeloid malignancies
2009, Cancer Genetics and CytogeneticsCitation Excerpt :Finally, this region is known to be involved in diverse congenital malformation syndromes [20]. Fluorescence in situ hybridization (FISH) studies in several cases of B-cell precursor ALL or Burkitt lymphoma with gain of 1q revealed a common duplicated region of 93 kb at band 1q21.2, where putative oncogenes or tumor suppressor genes are mapped (SF3B4, OTUD7B, and MTMR11) [8]. Another candidate gene in possible association with neoplasm development in this region is ARNT, in 1q21 [11,21].
Jumping translocations in hematological malignancies: a cytogenetic study of five cases
2008, Cancer Genetics and CytogeneticsCitation Excerpt :The cytogenetically normal karyotype at diagnosis and the detection of JT almost 1 year after diagnosis suggest that JT could not contribute to the pathogenesis of AML-M1. In case 2, involving the young patient with BL, the initial chromosomal abnormality was t(8;14)(q24;q32), while partial duplication of chromosome 1q was the secondary aberration, which is the most frequent secondary change associated with t(8;14)(q24;q32) in BL and appears to be linked to disease progression [13–16]. JT of 1q to chromosomes 13q, 14p, 18q, and 21q seem to be created after duplication of 1q, and at the time, it was determined that the patient already had a very aggressive clinical course (Fig. 2, A and B).