PREFERENTIAL CLUSTERING OF CHROMOSOMAL BREAKPOINTS IN BURKITT LYMPHOMAS AND L3-TYPE ACUTE LYMPHOBLASTIC LEUKEMIAS WITH A T(8 14) TRANSLOCATION/

We have analyzed the type of MYC/IG heavy-chain locus (IGH) rearrangem ent present in 15 patients affected by t(8;14)-positive primary Burkit t's lymphoma or acute lymphoblastic leukemia of the L3 type in an atte mpt to map in detail the locations of the chromosome 8 and chromosome 14 breakpoints. The almost constant position of the chromosome 8 break point (within or immediately 5' of the MYC gene) together with two dis tinct clusters of breakpoints on chromosome 14 resulted in two main ty pes of MYC/IGH (present in 12 of 15 cases). In the first type (six cas es), the MYC gene or at least its coding portion was joined with the J H region on chromosome 14, whereas in the second, present in another s ix cases, the MYC gene and the Calpha1 region were juxtaposed. Physica l linkage between the translocated MYC and a known enhancer element of the IGH locus is the common feature in the two types of rearrangement , suggesting that a high-level constitutive expression plays a promine nt role in MYC activation. Interestingly, the chromosome 14 break site within the switch alpha1 region, which has been only occasionally des cribed in other cases, is present in 40% of our patients, suggesting t he existence of preferential breakpoint cluster regions in cases of si milar geographic origin. (C) 1993 Wiley-Liss, Inc.