Bcl-2 initiates a new category of oncogenes: regulators of cell death

PECIFIC CHROMOSOMAL translocations are recur-S rently found in distinct types of ma1ignan~ies.l.~ Indeed, many of these interchromosomal translocations are essentially pathognomonic for a given tumor. The molecular cloning of chromosomal breakpoints has proven a rich source of novel proto-oncogenes. Experimental approaches indicate that deregulation of these genes represents a primary pathogenic event in the generation of tumors. Determining the normal developmental role of each gene promises to deliver insights into their oncogenic mechanism. The lessons provided from the study of one such oncogene, Bcl-2, argue that understanding the functional roles of genes found at breakpoints will have an enormous impact upon mammalian biology. Bcl-2 was discovered at the t( 14; 18)(q32;q21) breakpoint, the cytogenetic hallmark of human follicular l y m p h ~m a . ~-~ Bcl-2 is novel among proto-oncogenes in that it localizes to mitochondria.8 Moreover, Bcl-2 shows the unique functional role of blocking programmed cell death independent of affecting proliferation.