Journal
CANCER SCIENCE
Volume 113, Issue 11, Pages 3864-3876Publisher
WILEY
DOI: 10.1111/cas.15544
Keywords
aneuploidy; cancer progression; DNA FISH; gastric cancer; heterogeneity
Categories
Funding
- Japan Society for the Promotion of Science [15H02365, 15H05977, 18H04034, 19K16727]
- Vehicle Racing Commemorative Foundation
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Aneuploidy arises from chromosome segregation errors or chromosomal instability. This study analyzed gastric tumors and found that cancer cells exhibit a significant increase in aneuploid population, particularly in advanced cases. The expansion of aneuploid population is associated with p53 deficiency.
Aneuploidy arises from persistent chromosome segregation errors, or chromosomal instability. Although it has long been known as a hallmark of cancer cells, reduced cellular fitness upon induced ploidy alterations hinders the understanding of how aneuploidy relates to cancer development in the body. In this study, we used FISH analysis targeting centromeres to indicate ploidy changes, and quantitatively evaluated the ploidy statuses of gastric tumors derived from a total of 214 patients, ranging from early to advanced disease. We found that cancer cells reveal a marked elevation of aneuploid population, increasingly in cases diagnosed in advanced stages. The expansion of the aneuploid population is well associated with p53 deficiency, consistent with its essential role in genome maintenance. Comparisons among multiple locations within the tumor, or between the primary and metastatic tumors, indicated that cancer cells mostly retain their ploidy alterations throughout primary tumors, but metastatic tumors may consist of cells with either increased or decreased levels of aneuploidy. We also found that a notable proportion of polyploid cells are often already present in chronic gastritis epithelia. These observations underscore that chromosome-level variations are widespread in gastric cancers, shaping their genetic heterogeneity and malignant properties.
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