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KMID : 0350519930460020547
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Journal of Catholic Medical College
1993 Volume.46 No. 2 p.547 ~ p.558
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Allelic Deletions of Chromosomes and K-ras Point Mutations in Human Colorectal Cancer and Contiguous Tissues
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Abstract
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Human colorectal cancer is believed to result from a series of genetic and hereditary alterations such as gene amplification, point mutation, allelic deletion of tumor suppressor gene, change of oncogene products, leading to the progressive
disordering
of the normal mechanisms controlling growth. Among those genetic allelic deletion and point mutation were thought to be most important events. Allelic deletions of specific chromosomal regions contain tumor suppressor genes, whose product
normally
regulate growth and differentiation in a negative fashion and indirectly suppress neoplastic development. Allelic deletions of chromosomes can be studied using probes that detect restriction fragment length polymorphisms to detemine whether one
of
the
tumor parental alleles is lost specifically in the tumor DNA. There are about 11 kinds of ras oncogene point mutation on codon 12, 13 and 61. The frequency of mutation has been reported to be 40-50% in colorectal cancers.
To investigate the incidence pattern of allelic celetion of chromosomes 18q and 17p and ras point mutation, both paired RCR and retriction fragment length polymorphisms analysis using variable numbers of tandem repeat(VNTR) marker were done in 10
normal
mucosa tissues, 15 grossly normal contiguous tissues within 5 cm from cancer mass and 22 colorectal cancer tissues.
@ES The obtained results were as follows ;
@EN 1. There was no allelic deletion in normal mucosa tissue.
Incidences of allelic deletion of 18q OS-4 were 33.3%(5/15) in contiguous tissue and 40.9%(9/22) in cancer tissue. Incidences of allelic deletion of 17p pYNH37 were 26.6%(4/15) in contiguous tissue and 63.6%(14/22) in cancer tissue. Incidences of
allelic deletion of 17p pYNZ22 were 6.6%(1/15) in contiguous tissue and 27.2%(6/22) in cancer tissue.
2. Incidences of K-ras point mutations were 60%(9/15) in contiguous tissue, 77.2%(17/22) in cancer tissue and 80%(4/5) in Duke´s B, 76.4%(13/17) in Duke´s C. There was increasing tendency of mutation along with stage progression, but no
statistical
significance was noted.
3. Incidences of allelic deletion and K-ras point mutations showed no statistical difference between cancer tissue and contiguous tissue in cellular differentiation and tumor location.
4. Incidence of K-ras point mutation showed the tendency to be higher than that of allelic deletion in contiguous tissue, but there was no statistical difference. There was also no statistical difference between incidences of allelic deletion
and
K-ras
point mutaion in colorectal cancer tissue.
These results showed no statistical difference in incidences of 18q allelic deletion and K-ras point mutaions between contiguous tissue and cancer tissue. Allelic deletion of chromosomes 18q and 17p occurred more frequently in colorectal cancer
tissue
than in contiguous tissue.Genetic alteration did not have any relation with cellular differentiation or tumor location in the biologic behavior of the colorectal cancer.
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KEYWORD
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