Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14.
Previous studies have indicated the presence of a putative tumor suppressor gene on human chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have recently identified a minimally deleted region encompassing parts of two adjacent genes, termed LEU1 and LEU2 (leukemia-associated genes 1 and 2), and several additional transcripts. In addition, 50 kb centromeric to this region we have identified another gene, LEU5/RFP2. To elucidate further the complex genomic organization of this region, we have identified, mapped, and sequenced the homologous region in the mouse. Fluorescence in situ hybridization analysis demonstrated that the region maps to mouse chromosome 14. The overall organization and gene order in this region were found to be highly conserved in the mouse. Sequence comparison between the human deletion hotspot region and its homologous mouse region revealed a high degree of sequence conservation with an overall score of 74%. However, our data also show that in terms of transcribed sequences, only two of those, human LEU2 and LEU5/RFP2, are clearly conserved, strengthening the case for these genes as putative candidate B-CLL tumor suppressor genes.
Kapanadze
B
B
Radiumhemmets Research Laboratory, CCK, R8:03, Karolinska Hospital, Stockholm, S-171 76, Sweden.
Makeeva
N
N
Corcoran
M
M
Jareborg
N
N
Hammarsund
M
M
Baranova
A
A
Zabarovsky
E
E
Vorontsova
O
O
Merup
M
M
Gahrton
G
G
Jansson
M
M
Yankovsky
N
N
Einhorn
S
S
Oscier
D
D
Grandér
D
D
Sangfelt
O
O
D000818:Animals; D001483:Base Sequence; D002882:Chromosomes, Human, Pair 13; D003001:Cloning, Molecular; D017931:DNA Primers; D016147:Genes, Tumor Suppressor; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics; D017384:Sequence Deletion
D017931:DNA Primers; D009363:Neoplasm Proteins