Coincidence of synteny breakpoints with malignancy-related deletions on human chromosome 3.
We have found previously that during tumor growth intact human chromosome 3 transferred into tumor cells regularly looses certain 3p regions, among them the approximately 1.4-Mb common eliminated region 1 (CER1) at 3p21.3. Fluorescence in situ hybridization analysis of 12 mouse orthologous loci revealed that CER1 splits into two segments in mouse and therefore contains a murine/human conservation breakpoint region (CBR). Several breaks occurred in tumors within the region surrounding the CBR, and this sequence has features that characterize unstable chromosomal regions: deletions in yeast artificial chromosome clones, late replication, gene and segment duplications, and pseudogene insertions. Sequence analysis of the entire 3p12-22 revealed that other cancer-associated deletions (regions eliminated from monochromosomal hybrids carrying an intact chromosome 3 during tumor growth and homozygous deletions found in human tumors) colocalized nonrandomly with murine/human CBRs and were characterized by an increased number of local gene duplications and murine/human conservation mismatches (single genes that do not match into the conserved chromosomal segment). The CBR within CER1 contains a simple tandem TATAGA repeat capable of forming a 40-bp-long secondary hairpin-like structure. This repeat is nonrandomly localized within the other tumor-associated deletions and in the vicinity of 3p12-22 CBRs.
Microbiology and Tumor Biology Center, Karolinska Institute, Box 280, 171 77 Stockholm, Sweden. maria.kost-alimova@mtc.ki.se
Maria
M
Kost-Alimova
Hajnalka
H
Kiss
Ludmila
L
Fedorova
Ying
Y
Yang
Jan P
JP
Dumanski
George
G
Klein
Stefan
S
Imreh
D000818:Animals; D001483:Base Sequence; D002872:Chromosome Deletion; D018244:Chromosomes, Artificial, Yeast; D002893:Chromosomes, Human, Pair 3; D017931:DNA Primers; D006801:Humans; D051379:Mice
D017931:DNA Primers