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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A071
Knowledge of genomic changes accompanying progression from colorectal adenoma
to carcinoma within individual tumors is limited. The aim of the present
study was to compare chromosome aberrations in pre-invasive (adenomatous, A)
and invasive (carcinomatous, C) components of malignant polyps. CGH analysis
showed a higher degree of randomness of chromosome aberrations in A compared
to C. This may be explained by the hypothesis that adenomas consist of
multiple genetically different subclones, from one of which carcinoma
develops. Indeed we found that C often harboured only partly the same changes
as the A; sometimes some extra changes were acquired, and sometimes lost
(common changes range 55% - 11%). K-ras mutation analysis of eight pairs
showed 6 pairs as wildtype in both components, one pair wildtype in the A and
mutated in the C, and one pair mutated in the A and wildtype in the C.
In order to eliminate the influence of random genetic changes in the
evaluation of chromosomal abnormalities, we focussed at those that frequently
occur in carcinomas: gain of 8q, 13q, 20q, and loss of 8p, 17p and 18q.
Among these events, loss of 17p was always retained and sometimes acquired
in the C (75% in A, 93% in C), and gain of 8q and 13q increased remarkably
from A to C (13% to 27%, and 27% to 47%, respectively), suggesting that these
alterations are important for the transition from adenoma to carcinoma. The
present data do not seem to support a prominent role for K-ras mutation at
this stage.
LOSS OF 17P AND GAIN OF 8Q AND 13Q MARK THE TRANSITION FROM ADENOMA TO
CARCINOMA IN COLORECTAL MALIGNANT POLYPS
Hermsen M, Weiss MM, Postma C, Meuwissen SGM, Meijer GA, Giaretti W,
Baak JPA
Department of Pathology, Academic Hospital Vrije Universiteit, Amsterdam,
Netherlands