Loss of fragile histidine triad gene expression in advanced lung cancer is consequent to allelic loss at 3p14 locus and promoter methylation

Molecular Cancer Research : MCR
Anjilna WaliDigambar Behera

Abstract

The fragile histidine triad (FHIT) gene located at the 3p14.2 locus plays an important role in the pathogenesis of lung cancer. The objective of this study was to analyze loss of heterozygosity and FHIT gene methylation status and correlate them to fhit expression. Bronchoscopically obtained lung biopsies from 30 cases of histologically proven carcinoma of the lung in stage III were assessed for the alterations in the FHIT gene. Fhit protein expression was determined by immunohistochemistry, and transcript levels were determined by reverse transcription-PCR. Microsattelite alterations and methylation status of the Fhit gene promoter was determined by PCR. Loss of heterozygosity at the 3p14 locus was observed in all the 30 cases at least by one of the three microsatellite polymorphic markers. The FHIT gene promoter showed complete methylation in 37% cases and partial methylation in 47% cases, and 16% cases showed no promoter methylation. FHIT full-length coding region (exons 5-9) transcripts were present in eight cases (26.6%), and aberrant transcripts were additionally seen in four cases. Loss of FHIT mRNA expression correlated to FHIT promoter methylation but not to loss of heterozygosity at the 3p14 locus. There was a strong ...Continue Reading

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Citations

Jan 29, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chun-Hua DaiJian-Rong Wu
Dec 20, 2008·American Journal of Respiratory and Critical Care Medicine·Carla VerriUNKNOWN EUELC Consortium
May 28, 2013·The International Journal of Biological Markers·Ping ChenXing-Ping Tong
Nov 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Omar KujanPhilip Sloan

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