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Leukemogenesis

Meiotic origin of trisomy in neoplasms: evidence in a case of erythroleukaemia

Leukemia volume 15, pages 971–975 (2001)Cite this article

Abstract

Trisomic cells in neoplasms may represent abnormal clones originated from a tissue-confined mosaicism, and arise therefore by a meiotic error. We report on a 16-month-old child with erythroleukaemia (AML-M6), whose marrow karyotype at onset was 48,XX,del(13)(q12q14),del(14)(q22q32),+21,+21. The parental origin of the supernumerary chromosomes 21 was investigated by comparing 10 polymorphic loci scattered along the whole chromosome on the patient's marrow and her parents’ leukocytes. Three loci were informative for the presence of three alleles, two of which were of maternal origin; two further loci showed a maternal allele of higher intensity. Lymphocytes and skin fibroblasts showed a normal karyotype, and molecular analysis on leukocytes at remission, buccal smear and urinary sediment cells consistently showed only one maternal allele, whereas neonatal blood from Guthrie spot showed two maternal alleles as in the marrow. An accurate clinical re-evaluation confirmed a normal phenotype. Our results indicate that tetrasomy 21 arose from a marrow clone with trisomy 21 of meiotic origin. To the best of our knowledge, this is the first evidence that supernumerary chromosomes in neoplastic clones may in fact be present due to a meiotic error. This demonstrates that a tissue-confined constitutional mosaicism for a trisomy may indeed represent the first event in multistep carcinogenesis.

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Acknowledgements

We thank ABEO-Liguria for technical support. CCD and PowerGene Systems (Perceptive Scientific Instruments, UK) were a gift from AICODS (Vésenaz, CH). This work was supported by IGG grant ‘Studio delle anomalie cromosomiche nei tumori solidi pediatrici’ and by grants from MURST-COFIN 2000 to CD and FP. CM is a research fellow supported by Eredità Laura Capursi. DNA samples were stored thank to a Telethon grant (C30) to CD for the Cell and DNA Bank.

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Authors and Affiliations

  1. Biologia Generale e Genetica Medica, Università di Pavia, Pavia, Italy

    A Minelli, C Olivieri & C Danesino

  2. Divisione di Ematologia ed Oncologia Pediatrica, Istituto Giannina Gaslini, Genova, Italy

    C Morerio, C Panarello, C Rosanda & E Lanino

  3. Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Sezione di Biologia e Genetica, Università dell'Insubria, Varese, Italy

    E Maserati, L Bonvini & F Pasquali

  4. Divisione di Oncoematologia Pediatrica, Dipartimento di Pediatria, Università di Padova, Padova, Italy

    A Leszl

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  1. A Minelli
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Minelli, A., Morerio, C., Maserati, E. et al. Meiotic origin of trisomy in neoplasms: evidence in a case of erythroleukaemia. Leukemia 15, 971–975 (2001). https://doi.org/10.1038/sj.leu.2402123

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