hCDC4 and Genetic Instability in Cancer

Abstract

About twenty years ago, scientists began to discover that colorectal cancers are caused by the sequential acquisition of genetic alterations in specific genes. To this day, we are still dissecting the genome of colorectal cancers to identify specific “culprit” genes that play a role in tumorigenesis. At the same time, we have more recently begun to turn our attention to the features of cancer cells that distinguish them from normal cells and that may be targeted therapeutically. Aneuploidy is one such hallmark of cancers, but its role in tumorigenesis is heretofore undetermined. Our efforts have focused on elucidating the fundamental mechanisms underlying aneuploidy. The assertion that a genetic basis for aneuploidy would imply its importance in tumorigenesis, and consequently make it a potential therapeutic target, represents the rationale for our pursuit of this line of research. For the last few years, we have been trying to determine whether there is a genetic cause underlying this attribute of cancers. Our recently published work entitled, “Inactivation of hCDC4 can cause chromosomal instability,” attempts to address this issue and raises more questions about the cause, mechanism, timing, and therapeutic potential of genetic instability.1