Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma
Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma
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DOI：
10.1038/sj.onc.1208136
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发表时间：
2004-12-02
期刊：
影响因子：
8
通讯作者：
Seto, M
中科院分区：
文献类型：
--
作者：
Kameoka, Y;Tagawa, H;Seto, M
3p臂缺失已在多种实体肿瘤中检测到，但迄今为止尚未有研究调查弥漫性大b细胞淋巴瘤（DLBCL）中的这种缺失。最近，我们通过全基因组阵列-比较基因组杂交（CGH）证明，在大约30%的DLBCL病例中，3p14.2缺失。为了更详细地检查3p14.2位点的基因组损失，我们使用了3p14.2的contig BAC阵列，发现12个DLBCL样本显示了损失。所有缺失区域都位于脆弱组氨酸三联体（FHIT）基因内，最常见的缺失区域位于FHIT基因内含子4、5和外显子5所在区域的0.4 Mbp。转录本的伴随分析表明，FHIT基因在31%的DLBCL样本中被异常转录，并且异常转录本的外显子丢失与基因组缺失相关。这些发现表明：(1)3q14.2基因组物质的丢失是FHIT基因外显子丢失的原因；(2)FHIT基因的基因组丢失是产生异常转录本的原因之一。
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.