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Acute Leukemias

Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary myelodysplastic syndrome and acute myeloid leukemia

Abstract

Fluorescence in situ hybridization and comparative genomic hybridization characterized 6p rearrangements in eight primary and in 10 secondary myeloid disorders (including one patient with Fanconi anemia) and found different molecular lesions in each group. In primary disorders, 6p abnormalities, isolated in six patients, were highly heterogeneous with different breakpoints along the 6p arm. Reciprocal translocations were found in seven. In the 10 patients with secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS), the short arm of chromosome 6 was involved in unbalanced translocations in 7. The other three patients showed full or partial trisomy of the 6p arm, that is, i(6)(p10) (one patient) and dup(6)(p) (two patients). In 5/7 patients with unbalanced translocations, DNA sequences were overrepresented at band 6p21 as either cryptic duplications (three patients) or cryptic low-copy gains (two patients). In the eight patients with cytogenetic or cryptic 6p gains, we identified a common overrepresented region extending for 5–6 megabases from the TNF gene to the ETV-7 gene. 6p abnormalities were isolated karyotype changes in four patients. Consequently, in secondary AML/MDS, we hypothesize that 6p gains are major pathogenetic events arising from acquired and/or congenital genomic instability.

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Acknowledgements

PAC and BAC clones were obtained from the Roswell Park Cancer Institute libraries RPCI-1, RPCI-3, RPCI-5 and RPCI-11, http://www.chori.org/BACPAC. RP5-1106L7 was kindly provided by Dr M Rocchi, University of Bari, Italy; cosmid Cah5 by Dr E Weiss, Ludwig Maximilians Universität, München, Germany; and clones RP1-22O11, RP1-99J17, RP1-162J16, RP1-124L9 and RP3-329A5 by Dr I Ragoussis King's College, London, UK. We thank Dr Geraldine Anne Boyd for assistance in preparing the manuscript. This work was supported by AIRC (Associazione Italiana Ricerca sul Cancro), CNR (Consiglio Nazionale delle Ricerche), MIUR (Ministero per l’Istruzione, l’Università e la Ricerca Scientifica), Fondazione Cassa di Risparmio, Perugia, Associazione ‘Sergio Luciani’, Fabriano, AULL (Associazione Umbra contro le Leucemie e Linfomi) Italy; and Belgian Programme of Interuniversity Poles of Attraction initiated by Belgian State, Prime Minister's Office, Science Policy Programming. BC is supported by a grant from FIRC (Fondazione Italiana per la Ricerca sul Cancro).

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La Starza, R., Aventin, A., Matteucci, C. et al. Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary myelodysplastic syndrome and acute myeloid leukemia. Leukemia 20, 958–964 (2006). https://doi.org/10.1038/sj.leu.2404208

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