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胃癌中DBC2基因的遗传分析。

Genetic analysis of the DBC2 gene in gastric cancer.

作者信息

Cho Yong Gu, Choi Byung Joon, Kim Chang Jae, Song Jae Hwi, Zhang Cao, Nam Suk Woo, Lee Jung Young, Park Won Sang

机构信息

Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

出版信息

Acta Oncol. 2008;47(3):366-71. doi: 10.1080/02841860701644094. Epub 2007 Sep 28.

Abstract

The DBC2 (Deleted in breast cancer, RhoBTB2) has been identified as a tumor suppressor gene that has growth inhibitory function. To investigate whether genetic alterations of the DBC2 gene are involved in the development of gastric cancer, we analyzed mutations and allelic loss in the DBC2 gene in 95 primary gastric cancers by PCR-SSCP, sequencing and LOH analysis. In the mutational analysis, we found one missense somatic mutation (CGG-->TGG, R275W) in the BTB/POZ domain of the gene in a patient with advanced gastric cancer and lymph node metastasis. In addition, we found one known polymorphism and three novel polymorphisms in the coding region of DBC2, which showed an amino acid change, and was detected in both the cancer cells and corresponding normal cells. On LOH analysis, 62 cases were heterozygous for at least one marker and 18 cases (29.0%) showed allelic loss at these markers. In conclusion, the mutations and allelic loss in the DBC2 gene are uncommon in gastric cancers in Korean patients. Further studies to identify the target gene at 8q21 responsible for the development of gastric cancer should be explored.

摘要

DBC2(乳腺癌缺失基因,RhoBTB2)已被确定为具有生长抑制功能的肿瘤抑制基因。为研究DBC2基因的遗传改变是否参与胃癌的发生发展,我们采用PCR-SSCP、测序及杂合性缺失(LOH)分析,对95例原发性胃癌中DBC2基因的突变和等位基因缺失情况进行了分析。在突变分析中,我们在1例伴有淋巴结转移的进展期胃癌患者的该基因BTB/POZ结构域中发现了1个错义体细胞突变(CGG→TGG,R275W)。此外,我们在DBC2编码区发现了1个已知多态性位点和3个新的多态性位点,这些多态性位点均导致氨基酸改变,且在癌细胞和相应正常细胞中均被检测到。在LOH分析中,62例患者至少有1个标记位点呈杂合状态,其中18例(29.0%)在这些标记位点出现等位基因缺失。总之,韩国患者胃癌中DBC2基因的突变和等位基因缺失并不常见。应进一步开展研究,以确定8q21上负责胃癌发生发展的靶基因。

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