Expression of aberrant functional and nonfunctional transcripts of the FHIT gene in Burkitt's lymphomas

Autor: Ferrer, Milagros, López-Borges, Susana, Lazo, Pedro A.
Jazyk: angličtina
Rok vydání: 1999
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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ISSN: 1098-2744
0899-1987
Popis: The 3p14.2 chromosome region, which contains the FHIT gene and the FRA3B fragile site, is frequently altered in carcinomas. We analyzed the expression of the FHIT gene in 21 Burkitt's lymphoma cell lines and normal lymphoid populations. Seventeen (80%) of these cell lines had a common aberrant FHIT transcript as well as the normal transcript. Exon 2 was often aberrantly spliced to several coding exons, skipping exons 3 and 4, which overlap FRA3B. Other aberrant transcripts lacked exons 4-7 or exons 5-8. Exon 5, which has the initiation codon, was the most commonly affected. In two cell lines, Raji and KK124, there were aberrant transcripts retaining only the coding exons, which were able to make a normal protein, as demonstrated by in vitro transcription-translation analysis. In these aberrant messages, the additional deletion of 11 nucleotides at the beginning of exon 10 resulted in loss of translation. The cell line Ramos did not have a normal transcript. Some transcripts had common insertions of unknown origin that replaced coding exons, mainly exons 6 and 7. None of these aberrant messages coded for a protein, whether normal or aberrant. Within an individual cell line, aberrant messages appeared to result from sequential splicing reactions of a transcriptional unit derived from one allele. There was no correlation between aberrant FHIT transcription and the type of Burkitt's lymphoma regarding chromosomal translocation or presence of Epstein-Barr virus. In normal tonsils, spleen, and peripheral blood lymphocytes, aberrant transcripts were not detected and might represent a very minor subpopulation if detectable.
MF and SL-B are recipients of fellowships from Instituto de Salud Carlos III and Comunidad de Madrid, respectively. This work was supported by a grant from Fondo de Investigación Sanitaria (FIS 98/ 0313) to PAL.
Databáze: OpenAIRE
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