Impact of chromosomal translocation and genomic instability on personalized medicine

structural exchanges between heterologous chromosomes. We recently reviewed the critical impact of chromosomal translocations on cancer diagnosis, prognosis and treatment [4]. Specific chromosomal translocations are often closely associated with subtypes of leukemia and lymphoma, which has greatly facilitated the diagnosis and stratification of patients for certain types of treatments [4]. A classic example is the t(9;22) translocation, which generates the BCR–ABL fusion product in chronic myelo genous leukemia (CML) patients [5]. The cancer cell-specific BCR–ABL fusion protein is a target of the therapeutic agent STI-571 (Gleevec), which induces remission in the vast majority of CML patients [6]. The efficacy of Gleevec in CML is an early and key success that cancer research has delivered in personalized medicine. The Gleevec story also exemplifies the essential contribution of basic research, which enabled discovery of the molecular mechanisms of leukemo genesis and development of targeted therapies for the disease. Another success of individualized therapy in leukemia is the use of all-trans retinoic acid [7] and arsenic trioxide [8–10] in acute promyelocytic leukemia patients harboring the t(15;17) translocation [11]. The t(15;17) translocation fuses a portion of the PML gene to the RARA gene to encode the PML–RARA fusion protein [12]. Combined therapy of all-trans retinoic acid and arsenic trioxide induces a high rate of remission and survival in the vast majority of acute promyelocytic leukemia patients [13]. Many clinics now routinely screen for these translocations, performing karyotyping and cytogenetic analyses of leukemia or lymphoma cells before a specific treatment is identified. These successful medical practices owe credit to the extensive basic and The concept of personalized medicine The term ‘personalized medicine’, in the context used today, first appeared in a Wall Street Journal article in 1999 (already implicating its potential economic impact), which later appeared in the Oncologist [1]. In 2008, the President’s Council of Advisors on Science and Technology published a report, ‘Priorities for Personalized Medicine’, which provided a comprehensive definition of personalized medicine and highlighted its potential to influence healthcare and economics [101]. In recent years, personalized medicine has gained much wider recognition in the scientific community [2]. An ongoing paradigm shift from standard medicine (one-size-fits-all) to personalized medicine can be attributed to two important factors. First is the increasing incidence of chronic diseases such as cancer or metabolic diseases that tend to display more variation in clinical presentation, rather than acute infectious diseases such as those caused by bacteria. Second are rapid advances in new ‘omics’ technologies, including genomics, proteomics and metabolomics, which enable better characterization of individual variation and profiling of clinical differences at the molecular level. Cancer research has been at the forefront of personalized medicine, largely because of the low treatment response rate in a majority of cancers, the intrinsic heterogeneity of cancers, successful examples of targeted cancer therapy, and recent advances in genomic approaches for cancer pathology [3].