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The gene-reduction effect of chromosomal losses detected in gastric cancers
Seung-Jin Hong1, Eun-Jung Jeon, Jung-Hwan Oh
1Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Background:
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.
Methods:
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).
Results:
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%).
Conclusions:
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.
Insights
Loss of heterozygosity (LOH) impacts gastric cancer staging. Intestinal-type cancers tolerate gene loss better than diffuse-type, with high-level LOH linked to metastasis.
Area of Science:
- Oncology
- Genetics
- Cancer Biology
Background:
- Loss of heterozygosity (LOH) is a key parameter in gastric cancer genetic staging.
- The cell-adverse effects of gene reduction influence LOH events.
Purpose of the Study:
- To investigate if cell-adverse effects limit LOH in diffuse- and intestinal-type gastric cancers.
- To compare LOH patterns between gastric cancer subtypes.
Main Methods:
- Examined LOH in 145 gastric cancer patients using 40 microsatellite markers.
- Analyzed eight cancer-associated chromosomes (3p, 4p, 5q, 8p, 9p, 13q, 17p, 18q).
Main Results:
- Gene-poor chromosomes with highly expressed genes were common.
- Diffuse-type cancers showed frequent baseline LOH; intestinal-type cancers lost chromosome 17.
- High-level LOH correlated with intestinal/mixed differentiation and disease relapse.
Conclusions:
- Gastric cancer subtypes differ in tolerance to gene reduction effects.
- High-dose gene loss is associated with hematogenous metastasis in gastric cancer.
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