Related Experiment Video
Updated: Aug 21, 2026
Capturing Common Fragile Site Breaks by Native γH2A.X ChIP
Published on: January 24, 2025
Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell
Yoshihiro Kameoka1, Hiroyuki Tagawa, Shinobu Tsuzuki
1Division of Molecular Medicine, Aichi Cancer Center Research Institute, Aichi, Japan.
Abstract:
Deletions of the 3p arm have been detected in various solid tumors, but no study to date has investigated this deletion in diffuse large B-cell lymphoma (DLBCL). Recently, we demonstrated that 3p14.2 was deleted in approximately 30% of DLBCL cases by use of a genome-wide array-comparative genomic hybridization (CGH). For a more detailed examination of the genomic losses at 3p14.2, here we made use of contig BAC array for 3p14.2, and found that 12 DLBCL samples displayed losses. All of the deleted regions were located within the fragile histidine triad (FHIT) gene, and the most frequent region of loss was mapped to 0.4 Mbp of the region encompassing the introns 4 and 5 and exon 5 of the FHIT gene. Concomitant analysis of transcripts showed that the FHIT gene was aberrantly transcribed in 31% of the DLBCL samples examined and that the lost exons of the aberrant transcripts were correlated with genomic deletions. These findings indicate that (1) loss of genomic material at 3q14.2 is responsible for exon losses of the FHIT gene, and (2) genomic loss of the FHIT gene is one of the causes of the generation of aberrant transcripts.
Insights
Genomic deletions in the 3p14.2 region, specifically within the fragile histidine triad (FHIT) gene, are linked to aberrant FHIT gene transcription in diffuse large B-cell lymphoma (DLBCL). This study highlights FHIT gene loss as a factor in DLBCL development.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Deletions on the 3p chromosome arm are observed in various solid tumors.
- The role of 3p deletions in diffuse large B-cell lymphoma (DLBCL) has not been previously studied.
Purpose of the Study:
- To investigate genomic losses at 3p14.2 in DLBCL.
- To examine the association between these deletions and the fragile histidine triad (FHIT) gene.
- To determine the impact on FHIT gene transcription.
Main Methods:
- Genome-wide array-comparative genomic hybridization (CGH) was initially used to identify 3p14.2 deletions in DLBCL.
- A targeted contig BAC array was employed for detailed analysis of 3p14.2 genomic losses.
- Transcriptional analysis was performed to assess FHIT gene expression.
Main Results:
- Approximately 30% of DLBCL cases showed deletions at 3p14.2.
- All identified deletions were located within the FHIT gene, with a common region encompassing introns 4-5 and exon 5.
- Aberrant FHIT gene transcription was observed in 31% of DLBCL samples, correlating with genomic deletions.
Conclusions:
- Genomic losses at 3q14.2 directly cause exon losses in the FHIT gene.
- FHIT gene deletion is a contributing factor to the generation of aberrant FHIT transcripts in DLBCL.
