Profiling chromosomal-level variations in gastric malignancies.
Tetsuya NegotoMinji JoIzuma NakayamaMotohiro MoriokaKengo TakeuchiHiroshi KawachiToru HirotaPublished in: Cancer science (2022)
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.
Keyphrases
- induced apoptosis
- copy number
- genome wide
- small cell lung cancer
- single cell
- end stage renal disease
- squamous cell carcinoma
- cell cycle arrest
- ejection fraction
- helicobacter pylori
- newly diagnosed
- chronic kidney disease
- endoplasmic reticulum stress
- oxidative stress
- emergency department
- peritoneal dialysis
- drug induced
- gene expression
- patient safety
- prognostic factors
- cancer therapy
- body composition
- lymph node metastasis
- young adults
- squamous cell
- helicobacter pylori infection
- drug delivery
- quality improvement