Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
BMC Gastroenterol. 2010 Nov 20;10:138. doi: 10.1186/1471-230X-10-138.
The level of loss of heterozygosity (LOH) that reduces a gene dose and exerts a cell-adverse effect is known to be a parameter for the genetic staging of gastric cancers. This study investigated if the cell-adverse effect induced with the gene reduction was a rate-limiting factor for the LOH events in two distinct histologic types of gastric cancers, the diffuse- and intestinal-types.
The pathologic specimens obtained from 145 gastric cancer patients were examined for the level of LOH using 40 microsatellite markers on eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p and 18q).
Most of the cancer-associated chromosomes were found to belong to the gene-poor chromosomes and to contain a few stomach-specific genes that were highly expressed. A baseline-level LOH involving one or no chromosome was frequent in diffuse-type gastric cancers. The chromosome 17 containing a relatively high density of genes was commonly lost in intestinal-type cancers but not in diffuse-type cancers. A high-level LOH involving four or more chromosomes tended to be frequent in the gastric cancers with intestinal and mixed differentiation. Disease relapse was common for gastric cancers with high-level LOH through both the hematogenous (38%) and non-hematogenous (36%) routes, and for the baseline-level LOH cases through the non-hematogenous route (67%).
The cell-adverse effect of gene reduction is more tolerated in intestinal-type gastric cancers than in diffuse-type cancers, and the loss of high-dose genes is associated with hematogenous metastasis.
杂合性缺失（LOH）的水平降低了基因剂量并产生细胞不良效应，已知这是胃癌遗传分期的一个参数。本研究调查了在两种不同组织学类型的胃癌（弥漫型和肠型）中，基因减少引起的细胞不良效应是否是 LOH 事件的限速因素。
对 145 例胃癌患者的病理标本进行了 8 条癌症相关染色体（3p、4p、5q、8p、9p、13q、17p 和 18q）上 40 个微卫星标记物的 LOH 水平检测。
大多数癌症相关染色体属于基因贫乏染色体，含有少数高度表达的胃特异性基因。弥漫型胃癌中常存在涉及一个或无染色体的基线水平 LOH。含有相对高密度基因的 17 号染色体在肠型胃癌中常见丢失，但在弥漫型胃癌中不常见。高水平 LOH 涉及四个或更多染色体往往在具有肠型和混合分化的胃癌中更为常见。通过血液（38%）和非血液（36%）途径，高水平 LOH 的胃癌以及基线水平 LOH 病例（67%）的疾病复发较为常见。
基因减少的细胞不良效应在肠型胃癌中比在弥漫型胃癌中更容易耐受，高剂量基因的丢失与血行转移有关。
