Chromosomes in leukemia and beyond: from irrelevant to central players

Although it was definitely not obvious at first, consistent chromosomal translocations are major contributors to cellular transformation in some leukemias, lymphomas, sarcomas, prostate cancer, and other benign and malignant neoplasms. In the 50 years since the discovery of the Ph chromosome, the elucidation of recurring abnormalities has been an ongoing challenge that has evolved as new technologies allowed an ever more accurate definition of the precise changes in DNA resulting from these abnormalities. As we enter a new era of understanding enriched by gene expression studies, we still know little about the changes in the level of critical proteins, which may be the ultimate effectors of the genetic/epigenetic abnormalities in cancer. Despite remarkable progress in identifying both obvious chromosome abnormalities and subtle changes in DNA such as mutations and small copy-number variations, the impact of this knowledge has been variable. The challenge for the future is to enhance our ability to translate these genetic changes into effective therapies for other malignant diseases.