Kameoka Yoshihiro, Tagawa Hiroyuki, Tsuzuki Shinobu, Karnan Sivasundaram, Ota Akinobu, Suguro Miyuki, Suzuki Ritsuro, Yamaguchi Motoko, Morishima Yasuo, Nakamura Shigeo, Seto Masao
Division of Molecular Medicine, Aichi Cancer Center Research Institute, Aichi, Japan.
Oncogene. 2004 Dec 2;23(56):9148-54. doi: 10.1038/sj.onc.1208136.
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.
在各种实体瘤中均检测到3p臂的缺失，但迄今为止尚无研究对弥漫性大B细胞淋巴瘤（DLBCL）中的这种缺失进行调查。最近，我们通过全基因组阵列比较基因组杂交（CGH）证明，约30%的DLBCL病例中存在3p14.2缺失。为了更详细地研究3p14.2处的基因组缺失，我们在此使用了3p14.2的重叠群BAC阵列，发现12个DLBCL样本存在缺失。所有缺失区域均位于脆性组氨酸三联体（FHIT）基因内，最常见的缺失区域定位于包含FHIT基因第4和第5内含子以及第5外显子的区域的0.4 Mbp处。对转录本的伴随分析表明，在所检测的31%的DLBCL样本中，FHIT基因存在异常转录，且异常转录本中缺失的外显子与基因组缺失相关。这些发现表明：（1）3q14.2处基因组物质的缺失导致了FHIT基因外显子的缺失；（2）FHIT基因的基因组缺失是异常转录本产生的原因之一。
