BACKGROUND: The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas. METHODS: FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene. RESULTS: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours. CONCLUSIONS: Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.
BACKGROUND: The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas. METHODS:FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene. RESULTS: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours. CONCLUSIONS: Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.
Authors: David Velázquez-Fernández; Cecilia Laurell; Milena Saqui-Salces; Juan Pablo Pantoja; Fernando Candanedo-Gonzalez; Alfredo Reza-Albarrán; Armando Gamboa-Dominguez; Miguel F Herrera Journal: World J Surg Date: 2006-05 Impact factor: 3.352
Authors: Jie Cao; Xiao-Ping Chen; Wang-Lin Li; Jie Xia; Hong Du; Wei-Biao Tang; Hui Wang; Xi-Wen Chen; Huan-Qing Xiao; Yu-Yuan Li Journal: World J Gastroenterol Date: 2007-02-21 Impact factor: 5.742
Authors: Jie Cao; Xiaoping Chen; Wanglin Li; Jie Xia; Hong Du; Weibiao Tang; Shanming Chen; Hui Wang; Xiwen Chen; Huanqing Xiao; Yuyuan Li Journal: Front Med China Date: 2007-05-01
Authors: H Andachi; K Yashima; M Koda; K Kawaguchi; A Kitamura; A Hosoda; Y Kishimoto; G Shiota; H Ito; M Makino; N Kaibara; H Kawasaki; Y Murawaki Journal: Br J Cancer Date: 2002-08-12 Impact factor: 7.640