The Research Center for Medical Genomics and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, PR China.
Hum Pathol. 2012 Dec;43(12):2308-17. doi: 10.1016/j.humpath.2012.01.024. Epub 2012 Aug 16.
Loss of heterozygosity of 1p35-pter, 4q, and 18q is frequent in gastric carcinoma, suggesting that these regions harbor tumor suppressor genes. However, the differences in these genetic alterations between adenocarcinoma of the gastric cardia and adenocarcinoma of the distal stomach remain unclear. In this study, loss of heterozygosity at chromosomes 1p35-pter, 4q, and 18q were analyzed in adenocarcinoma of the gastric cardia and adenocarcinoma of the distal stomach samples acquired by laser capture microdissection. The expression of several tumor suppressor gene proteins, runt-related transcription factor 3 (1p36), annexin A10 (4q33), SMAD family member 4 (18q21.1), and deleted in colorectal carcinoma (18q21.3), was evaluated immunohistochemically. The adenocarcinoma of the distal stomach and adenocarcinoma of the gastric cardia lesions had a similar trend in total deletion frequency for chromosomes 1p35-pter (36.5% for adenocarcinoma of the distal stomach and 32.5% for adenocarcinoma of the gastric cardia), 4q (42.3% for adenocarcinoma of the distal stomach and 47.5% for adenocarcinoma of the gastric cardia), and 18q (38.5% for adenocarcinoma of the distal stomach and 45% for adenocarcinoma of the gastric cardia). However, loss of heterozygosity patterns were clearly different in the 2 adenocarcinomas. Deletion mapping indicated that 4q32.2-4q34.3, 18q21.2-21.31, 18q22.3-23, and 1p35.2-1p36.13 were involved in adenocarcinoma of the distal stomach, whereas 4q13.3-4q22.3, 4q31.21-4q32.2, 18q21.31-18q22.1, and 1p35.2-1p36.13 were involved in adenocarcinoma of the gastric cardia. Expression of ANXA10 (P = .038), SMAD family member 4 (P = .028), and deleted in colorectal carcinoma (P = .004) was less common in adenocarcinoma of the distal stomach than in adenocarcinoma of the gastric cardia. Expression of runt-related transcription factor 3 (P = .795) showed no significant difference in the 2 tumors. The tumors differed in the profile of genetic alterations and protein expression of these well-known tumor suppressor genes. The deleted regions defined in this study may harbor tumor suppressor genes relevant to adenocarcinoma of the gastric cardia.
杂合性缺失在胃癌中频繁发生于 1p35-pter、4q 和 18q，提示这些区域存在肿瘤抑制基因。然而，贲门腺癌和远端胃癌之间这些遗传改变的差异尚不清楚。本研究通过激光捕获显微切割获取贲门腺癌和远端胃癌样本，分析染色体 1p35-pter、4q 和 18q 的杂合性缺失，并免疫组化评估几个肿瘤抑制基因蛋白——Runt 相关转录因子 3（1p36）、膜联蛋白 A10（4q33）、SMAD 家族成员 4（18q21.1）和结直肠癌缺失基因（18q21.3）的表达情况。远端胃癌和贲门腺癌的总缺失频率在染色体 1p35-pter（远端胃癌为 36.5%，贲门腺癌为 32.5%）、4q（远端胃癌为 42.3%，贲门腺癌为 47.5%）和 18q（远端胃癌为 38.5%，贲门腺癌为 45%）方面具有相似趋势。然而，这两种腺癌的杂合性缺失模式明显不同。缺失图谱表明，4q32.2-4q34.3、18q21.2-21.31、18q22.3-23 和 1p35.2-1p36.13 参与了远端胃癌的发生，而 4q13.3-4q22.3、4q31.21-4q32.2、18q21.31-18q22.1 和 1p35.2-1p36.13 则参与了贲门腺癌的发生。膜联蛋白 A10（P =.038）、SMAD 家族成员 4（P =.028）和结直肠癌缺失基因（P =.004）的表达在远端胃癌中较贲门腺癌少见。Runt 相关转录因子 3（P =.795）的表达在这两种肿瘤中无显著差异。这些肿瘤在这些已知的肿瘤抑制基因的遗传改变和蛋白表达特征方面存在差异。本研究中定义的缺失区域可能存在与贲门腺癌相关的肿瘤抑制基因。
