The status of p53 in the metastatic progression of colorectal cancer.
In order to investigate the role of TP53 in tumour progression and metastasis, we analysed 33 liver metastases of colorectal carcinomas and 19 primary colon carcinomas from the same hospital with respect to mutational changes, loss of heterozygosity and expression of the TP53 tumour suppressor gene. Direct sequencing of PCR products corresponding to the coding region of TP53 revealed that 13 of 19 primary tumours (68%) and 23 of 33 liver metastases (70%) had mutations in the TP53 gene. The distribution of mutations along the coding region of TP53 was similar in liver metastases compared to primary tumours. Thus, codon specificity did not seem to be a relevant factor and cells carrying specific TP53 mutations seem to have no selective advantage in the metastasising process. Comparing our data with the mutational spectra found in other countries did not reveal differences in the distribution of mutations along the coding region. Most of the metastases analysed showed loss of heterozygosity (LOH, 9 of 12 cases, 75%) and strong nuclear staining in immunohistochemistry (10 of 17 cases, 59%). Furthermore, with respect to mRNA expression levels, tumours carrying TP53 mutations showed significantly higher p53 mRNA levels compared to those without TP53 mutations. Thus, regulation of p53 mRNA levels seems to be subject to selection processes in tumourigenesis.
Heide
I
I
Abteilung für Innere Medizin m. S. Hämatalogie und Onkologie, Klinikum Rudolf Virchow, Humboldt-Universität Berlin, Germany.
Thiede
C
C
Sonntag
T
T
de Kant
E
E
Neubauer
A
A
Jonas
S
S
Peter
F J
FJ
Neuhaus
P
P
Herrmann
R
R
Huhn
D
D
Rochlitz
C F
CF
D002872:Chromosome Deletion; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D009363:Neoplasm Proteins / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53