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

Abstract

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.

Characterization of aberrant FHIT transcripts in gastric adenocarcinomas

“…In cases 18, 24, and 26, their transcripts (A, B, C, or D) appeared to represent sequential processing for splicing out the intron sequence already inserted as a consequence of aberrant splicing, suggesting that sequential reactions of alternative splicing within a given tumor might be derived from a transcriptional unit in a single allele. Similar report has been described in Burkitt's lymphoma (Ferrer et al, 1999).…”

Analysis of the tumour suppressor genes, FHIT and WT-1, and the tumour rejection genes, BAGE, GAGE-1/2, HAGE, MAGE-1, and MAGE-3, in benign and malignant neoplasms of the salivary glands

“…This alteration shifts the reading frame and may lead to the synthesis of an aberrant truncated FHIT protein. Such insertions of non-coding sequences are rarely found in human carcinomas and were previously described in carcinomas from the oesophagus and the stomach, 1 in Burkitt lymphoma, 25 and in endometrial carcinoma. 18 In conclusion, FHIT splice variants are infrequent findings in normal salivary gland tissue, benign salivary gland tumours, and malignant salivary gland tumours.…”

Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with multiple myeloma

“…Low levels of fhit protein expression are also detected in these cancers, and methylation of the FHIT gene is one of the mechanisms responsible for the loss of its expression (14). Regarding hematological malignancies, abnormalities in the transcription and expression of the FHIT gene have been reported in malignant lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myeloproliferative disorder, and myelodysplastic syndrome (21–24). We demonstrated that the FHIT gene was frequently methylated in MM (44%).…”