Allelic imbalance and abnormal expression of FHIT in endemic nasopharyngeal carcinoma: association with clinicopathological features

Abstract

The FHIT gene is involved in the pathogenesis of many cancers. The aim of this study was to investigate allelic imbalance (AI) pattern at FHIT locus and alteration of FHIT gene in nasopharyngeal carcinoma (NPC) and analyzed potential correlation between AI, FHIT mRNA expression and clinicopathological factors. We examined AI, including loss of heterozygosity (LOH) and microsatellite instability (MSI), at FHIT locus in 41 cases of NPC by microsatellite analysis and FHIT gene status in 30 cases of NPC by nested reverse transcriptase-polymerase chain reaction and DNA sequencing. The frequencies of LOH and MSI at FHIT locus in NPC were 70.7% (29/41) and 36.6% (15/41), respectively. Thirteen of thirty (43.3%) NPCs exhibited aberrant FHIT transcripts. LOH and abnormal FHIT expression were correlated with advanced clinical stage and higher titers of immunoglobulin (Ig) A against Epstein-Barr virus capsid antigen (EBVCA-IgA) (p < 0.05). Abnormal FHIT expression was also correlated with tumor recurrence (p < 0.05). MSI was correlated with early clinical stage and higher titers of EBVCA-IgA (p < 0.05). AI at FHIT locus is a common event and contributes to genetic imbalance in NPC. The abnormalities of FHIT, presumably associated with genetic imbalance at FHIT locus, might be involved in the development and the tumor recurrence of NPC.