Deciphering how chromosomal mix-ups lead to tumors
Scientists do not fully understand the underlying genetic causes of lymphoma and leukemia. If they can identify the location and cause of errors in the genome, that knowledge could provide new therapeutic targets for treatment of disease.
IRP scientists led by Rafael Casellas, Ph.D., discovered that recurrent chromosomal rearrangements, or translocations, occur when broken strands of DNA from one chromosome are mistakenly joined with those of another, which can lead to uncontrolled cell growth or cancer. The researchers found that an enzyme called Activation Induced Deaminase (AID) plays a key role in promoting translocations.
The new findings helped clarify the origin of cancer-inducing translocations and identified AID as a potential therapeutic target to prevent the development of many human cancers.
Klein IA, Resch W, Jankovic M, Oliveira T, Yamane A, Nakahashi H, Di Virgilio M, Bothmer A, Nussenzweig A, Robbiani DF, Casellas R, Nussenzweig MC. Pavri R, Gazumyan A, Jankovic M, Di Virgilio M, Klein I, Ansarah-Sobrinho C, Resch W, Yamane A, Reina San-Martin B, Barreto V, Nieland TJ, Root DE, Casellas R, Nussenzweig MC. (2011). Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell. 147(1), 95-106.