Chromosome number and structure both are markedly stable in RER colorectal cancers and are not destabilized by mutation of p53.
Fourteen colorectal cancer cell lines, categorized according to the presence or absence of microsatellite instability, were further analysed for chromosomal stability by karyotyping. NonRER (microsatellite stable) cell lines typically displayed highly aberrant karyotypes with alterations not only of chromosome number but also of chromosome structure including chromosomal deletions, inversions, and translocations. RER (microsatellite unstable) cell lines, in contrast, displayed significantly fewer alterations of chromosome number. Moreover, RER cell lines also displayed significantly fewer cytogenetically evident alterations of chromosome structure. Compared to NonRER colon cancers, RER colon cancers are significantly less likely to have undergone chromosomal gain, loss, or breakage. Characterization of p53 gene status by gene sequencing was performed in an attempt to determine if p53 gene status correlated with the chromosomal stability of the RER cancers. Gene mutations in p53 were present in all of the NonRER colon cancers. However, p53 gene mutations were also found present in four of nine of the RER colon cancers. Unexpectedly, RER colon cancers bearing mutant p53 demonstrated the same stability of chromosome number, and the same stability of chromosome structure, as the RER colon cancers with wild-type p53. Therefore, in RER colon cancers specific p53 independent mechanisms actively maintain the stability of both chromosome number and structure.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J R
JR
Eshleman
G
G
Casey
M E
ME
Kochera
W D
WD
Sedwick
S E
SE
Swinler
M L
ML
Veigl
J K
JK
Willson
S
S
Schwartz
S D
SD
Markowitz
D002869:Chromosome Aberrations; D002875:Chromosomes / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000145:classification / Q000235:genetics*; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53