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Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia

Oncogene volume 18, pages 79–85 (1999)Cite this article

Abstract

Alterations of the recently cloned fragile histidine triad (FHIT) gene at chromosome 3p14.2 are frequent in a variety of solid tumours and cancer cell lines. Based on these findings, FHIT has been proposed as a putative tumour-suppressor gene. We evaluated the mRNA expression of the FHIT gene in samples from 55 patients with various haematological malignancies (21 AML, 8 CML, 10 CLL, seven low-grade and nine high-grade Non-Hodgkin's lymphomas), in a panel of 16 leukaemia cell lines, in normal mature haematopoietic cells of both myeloid and lymphoid lineage, as well as in CD34+ haematopoietic progenitor cells. Aberrant FHIT mRNA transcripts were observed in 14/16 (88%) leukaemia cell lines, 43/55 (78%) primary haematological neoplasms, but also in 17/22 (77%) normal controls. 1/16 (6%) cell lines and 7/55 (13%) neoplasms did not express any FHIT mRNA. cDNA sequencing revealed exonic deletions, small DNA insertions and combinations of both. Analysis of genomic DNA showed gene deletions in two myeloid leukaemia cell lines. In contrast to all normal types of haematopoietic cells, FHIT protein was clearly reduced or absent in 8/18 (44%) neoplastic samples tested. Our data indicate that whilst aberrant FHIT mRNA transcripts are seen both in normal and malignant cells, lack of FHIT protein is restricted to leukaemia. Absent FHIT protein expression might contribute to leukaemogenesis.

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Acknowledgements

We would like to thank Dr Nicole Schmitz and Dr Pius Lötscher for their help in establishing some of the techniques used, Dr F Joncourt for her assistance in sequencing, and Madeleine Oestreicher, Elisabeth Ischi as well as Karin Zbären for excellent technical assistance. This work was supported by grants from the Swiss National Foundation (31-43458.95), the Swiss Cancer League (KFS 156-9-1995) and the Bernese Foundation for Clinical Cancer Research.

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Authors and Affiliations

  1. Department of Clinical Research, University and Inselspital, Berne, Switzerland

    Uwe R Peters, Urs Hasse, Elisabeth Oppliger, Mario Tschan & Martin F Fey

  2. Institute of Medical Oncology, University and Inselspital, Berne, Switzerland

    Uwe R Peters & Martin F Fey

  3. Central Haematology Laboratory, University and Inselspital, Berne, Switzerland

    Andreas Tobler

  4. Department of Pathology, University of Geneva, Switzerland

    Bettina Borisch

  5. Section of Haematology/Oncology, University of Chicago Medical Center, Chicago, Illinois, USA

    S Tiong Ong & Feyruz V Rassool

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  1. Uwe R Peters
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Peters, U., Hasse, U., Oppliger, E. et al. Aberrant FHIT mRNA transcripts are present in malignant and normal haematopoiesis, but absence of FHIT protein is restricted to leukaemia. Oncogene 18, 79–85 (1999). https://doi.org/10.1038/sj.onc.1202256

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