Frequent silencing of fragile histidine triad gene (FHIT) in Burkitt's lymphoma is associated with aberrant hypermethylation

Genes, Chromosomes & Cancer
Azhar HussainKishor Bhatia

Abstract

The fragile histidine triad (FHIT) gene, a potential tumor-suppressor gene, is frequently inactivated in multiple human cancers. However, the FHIT gene remains largely unexplored in Burkitt's lymphoma (BL). Hence, we assessed whether loss of FHIT expression occurs in BL, and, if so, what is the mechanism of such loss. Lack of protein expression was observed in 50% of BL cell lines. Methylation-specific polymerase chain reaction (MSP) showed that 45% of BL cell lines carried aberrantly methylated FHIT alleles. Sequencing of bisulfite-treated DNA confirmed these data and indicated a very high density of methylation in all methylated alleles. Real-time, quantitative reverse-transcription PCR analysis indicated that attenuation of full-length FHIT transcription was correlated with methylation. Sequencing of transcripts illustrated that aberrant transcription resulting in loss of FHIT exons occurred more commonly in BL containing unmethylated FHIT genes. However, such transcripts often coexisted with full-length FHIT transcripts. Not surprisingly, therefore, loss of FHIT protein in BL correlated with CpG island methylation, rather than with aberrant transcription. FHIT methylation also was detected in 31% (16 of 51) of the primary B...Continue Reading

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Citations

May 12, 2009·Seminars in Cancer Biology·Hans Helmut NillerJanos Minarovits
Oct 17, 2009·British Journal of Haematology·Daniela CapelloFrancesco Bertoni
Dec 21, 2016·International Journal of Cancer. Journal International Du Cancer·Mette Ø AgerbaekAli Salanti
Mar 11, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Karen E DeffenbacherWing C Chan

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