troduced 5' to a D1/D2/J81 intermediate rearrange- 
ment. Symmetrically, the der (14) breakpoint corre- 
sponded to a perfect signal joint between the D8 1 
heptamer signal and a fortuitous heptamer signal 
from lip 15. Unlike other translocations, this event 
activates multiple, apparently distinct transcripts 
from both sides of the der (14) breakpoint. The 
' analysis of one deregulated gene (T^^^-l) that en- 
codes a 156-amino acid protein containing internal 
repeats w^ith zinc finger motifs has been completed. 
B. t(10;14)(q24;qll) breakpoint and deregulated 
Tcl-3. Similarly, this translocation in T-ALL intro- 
duces chromosome segment 10q24 into an inter- 
mediate 8 TCR rearrangement at l4qll. A locus 
distinct from terminal deoxynucleotidyl transferase 
was found near the clustered breakpoint region on 
10q24. Evolutionarily conserved regions surround- 
ing the 10q24 breakpoint were examined for tran- 
scriptional activity. A locus on the der (14) chro- 
mosome is markedly deregulated, resulting in 
abundant amounts of a 2.9 kb mRNA from the can- 
didate proto-oncogene 7c/-3. 
III. Mapping and Walking Within Human Chro- 
mosome Segments Utilizing Yeast Artificial Chromo- 
some Clones. 
The vast majority of the chromosomal aberra- 
tions associated with cancer or developmental syn- 
dromes are located a considerable distance from 
known genes. This observation emphasizes the 
need to develop technologies that bridge the gap 
between cytogenetic and routine phage and cosmid 
PUBLICATIONS 
cloning. Well-characterized large genomic clones 
obtained from yeast artificial chromosome (\AC) li- 
braries provide the framework to localize genes and 
approach genetic disease. Universally applicable ap- 
proaches to establish authenticity, localize and ori- 
ent internal genes, map restriction sites, and rescue 
the distal ends of large human genomic DNA in- 
serts were developed. Human chromosome seg- 
ment 18q21.3 was selected as a model. Molecular 
cloning of this segment was initiated by characteriz- 
ing three plasminogen activator inhibitor-2 (PAI-2) 
clones (290, 180, and 60 kb in size) isolated from a 
\AC library. Comparison of \AC and bacteriophage 
X genomic DNA clones confirmed the fidelity of the 
PAI-2 locus. Detailed rare cutting restriction maps 
could be generated utilizing ramped contour- 
clamped homogeneous electric field electrophore- 
sis. The PAI-2 locus could be located and oriented 
within the \ACS. Moreover, both left and right ends 
of the YAC genomic DNA inserts were rescued by 
amplifying circularized cloning sites with an in- 
verted form of the polymerase chain reaction. 
These unique terminal genomic DNA fragments 
were used to rescreen the Y\C library and isolate 
overlapping clones that extend the map. These ap- 
proaches will enable neighboring loci to be linked 
definitively and establish the feasibility of using \AC 
technology to clone and map chromosomal seg- 
ments. 
Dr. Korsmeyer is also Associate Professor of Medi- 
cine and of Microbiology and Immunology at Wash- 
ington University School of Medicine and Associate 
Physician at Barnes Hospital, St. Louis. 
Books and Chapters of Books 
Felix, C.A., and Korsmeyer, S.J. 1988. Immunology and molecular biology of lymphoma. In Thoracic Oncol- 
ogy (Roth, J.A., Ruckdeschel, J.C., and Weisenburger, T.H., Eds.). Philadelphia, PA: Saunders, pp 430-447. 
Korsmeyer, S.J. 1989- Immunoglobulin genes in human lymphoid neoplasms. In Immunoglobulin Genes 
(Honjo, T, Alt, F.W , and Rabbitts, T.H., Eds.). London: Academic, pp 233-255. 
Articles 
Brownstein, B.H., Silverman, G.A. , Little, R.D., Burke, D.T., Korsmeyer, S.J. , Schlessinger, D., and Olson, M.V 
1989. Isolation of single-copy human genes from a library of yeast artificial chromosome clones. Science 
244:1348-1351. 
Carroll, WL., Yu, M., Link, M.R, and Korsmeyer, S.J. 1989. Absence of Ig V region gene somatic hypermutation 
in advanced Burkitt's lymphoma. J Immunol 143:692-698. 
Cogne, M., Bakhshi, A., Korsmeyer, S.J. , and Guglielmi, P 1988. Gene mutations and alternate RNA splicing 
result in truncated Ig L chains in human 7 H chain disease. J Immunol 141:1738-1744. 
Continued 
410 
