CLONING AND CHARACTERIZATION OF THE HUMAN T(36)(P14P11) TRANSLOCATIONBREAKPOINT ASSOCIATED WITH HEMATOLOGIC MALIGNANCIES

The t(3;6)(p14;p11) chromosome translocation was identified in a famil y in which three members developed hematologic malignancies. To help c haracterize the region on chromosome 3 surrounding this translocation breakpoint, two flanking lambda clones, MS156 and MJ1525, were linked by pulsed-field gel electrophoresis to the same 510-kb NotI fragment o n chromosome 3. MS156 was localized to a region proximal to the breakp oint of a der(3) chromosome somatic cell hybrid (derived from the t(3; 6) cell line), and MJ1525 localized distal to the breakpoint. MJ1525 w as used to screen the CEPH yeast artificial chromosome (YAC) library, which revealed a YAC, 195F3, that spanned the breakpoint. Subcloning i nto Lambda DASH II and production of a contiguous array of overlapping lambda clones revealed a clone, L17, that spanned the breakpoint. A r are restriction endonuclease map for the YAC 195F3 was constructed, an d multiple clusters of rare restriction sites within the YAC were iden tified, possibly indicating the disruption of a gene by the t(3;6) tra nslocation breakpoint.