The more the messier: centrosome amplification as a novel biomarker for personalized treatment of colorectal cancers

Abstract

Colon cancer is currently the third most common cancer and second most fatal cancer in the United States, resulting in approximately 600,000 deaths annually. Though colorectal cancer death rates are decreasing by about 3% every year, disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis, the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments. Colon carcinogenesis is notably a slow process that can take decades. Known factors that contribute to the development of colon cancer are mutational, epigenetic and environmental, and risk factors include age, history of polyps and family history of colon cancer. Colorectal cancers exhibit heterogeneity in their features and are often characterized by the presence of chromosomal instability, microscopic satellite instability, or CpG island methylator phenotype. In this review, we propose that centrosome amplification may be a widespread occurrence in colorectal cancers and could potently influence tumor biology. Moreover, the quantitation of this cancer-specific anomaly could offer valuable prognostic information and pave the way for further customization of treatment based on the organellar profile of patients. Patient stratification models that take into account centrosomal status could thus potentially reduce adverse side effects and result in improved outcomes for colorectal cancer patients.

Keywords: aneuploidy; biomarker; centrosome amplification; chromosomal instability; colorectal cancer; prognostic.

Fig. 1. Colorectal carcinomas show rampant centrosome amplification.

Representative immunofluorescence confocal micrographs showing centrosome profiles in normal adjacent (left panel) and high-grade carcinoma (right panel). Centrosomes and microtubules were visualized by immunostaining for γ-tubulin (green) and α-tubulin (red), respectively. DNA was 4,6-diamidino-2-phenylindole (DAPI) stained (blue). Both numerical and structural centrosome amplification are evident in the high-grade carcinoma. Scale bar, 5 μm. A: normal; B: high-grade carcinoma.