Genomic loci susceptible to replication errors in cancer cells.
Microsatellite instability due to a deficiency in DNA mismatch repair is characteristic of a replication error (RER) phenotype. This widespread genomic instability is well documented in hereditary non-polyposis colon cancer (HNPCC) as well as subsets of sporadic carcinomas. Features of the RER phenotype such as the early appearance in tumour development and better prognosis of RER+ colorectal tumours render its examination important for cancer patients. Recently, we identified four loci that were shown to be highly susceptible to RER in cancer cells. Here, we used these loci to detect the RER phenotype in sporadic carcinomas of colon, breast, lung, endometrium and ovary. Replication errors revealed by these four markers followed the same tumour specificity as observed in HNPCC patients. In particular, 24% (6/25) of colorectal, 33% (4/12) of endometrial and 17% (2/12) of ovarian cancers displayed the RER phenotype characterized by an increased allelic mobility, whereas none of the breast (n = 22) and the lung (n = 27) carcinomas were found to be unstable. Assaying RERs sensitive loci provides us with a useful diagnostic tool for HNPCC-like sporadic tumours.
Krajinovic
M
M
Charles Bruneau Cancer Centre, Research Centre, Ste-Justine Hospital, Montreal, Quebec, Canada.
Richer
C
C
Gorska-Flipot
I
I
Gaboury
L
L
Novakovic
I
I
Labuda
D
D
Sinnett
D
D
D003110:Colonic Neoplasms / Q000235:genetics; D004260:DNA Repair; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction
D005819:Genetic Markers