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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple genetic alterations were investigated in colorectal cancer, including changes in DNA content, mutations in ras oncogenes, and deletions involving chromosomes 5, 17, and 18. A non-random association of deletions and mitotic abnormalities by site was seen, with both types of alterations occurring significantly more frequently in distal tumours. In contrast, the frequency of c-Ki-ras mutations did not differ between proximal and distal cancers. In addition, deletions were significantly associated with each other and with change in DNA content. The data provide strong support for the hypothesis that proximal and distal colon carcinoma might differ in the genetic mechanisms in their initiation and/or progression.
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PMID:Multiple genetic alterations in distal and proximal colorectal cancer. 256 52

Molecular genetic studies of tumor-specific allele loss, originally associated primarily with research regarding childhood hereditary cancers such as retinoblastoma and Wilms' tumors, only lately have been recognized as a relatively fast and fruitful way of locating cancer genes on human chromosomes. To date, over 25 different cancers have been tied to a gene (or genes) on a specific chromosome when this method has been used. During the past year alone, this approach has permitted detection of three genes involved in either hereditary or sporadic colorectal cancers. These three genes, located on chromosomes 5q, 17p, and 18q, are believed to belong to the newly described tumor suppressor (or growth suppressor) gene class, whose effects are opposite those of activated cellular oncogenes, which promote uncontrolled cell growth. Present studies, however, have not shown losses of any of these tumor suppressor genes to be correlated with the presence of activated ras genes in colorectal adenomas or carcinomas. During progression from adenoma to carcinoma, ras gene mutations and 5q allelic deletions are likely to be earlier events, whereas allelic losses from chromosomes 18q and 17p seem to occur more often in advanced tumors. Involvement of the genes on 5q (FAP) and 18q (Lynch syndrome II) in hereditary colon cancer syndromes is supported by linkage studies, but their respective roles (as well as that of the gene on 17p) in familial and sporadic colorectal cancer remain to be precisely defined. Probable isolation of these three genes by molecular cloning within the next few years will help elucidate their specific biologic functions. It will also permit early detection, and thus prevention, of some familial colon cancers (such as FAP), and possibly allow DNA marker-based separation of different colon cancer subtypes of similar histologic appearance.
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PMID:Molecular genetic studies of colon cancer. 264 66

The expression of oncogenes (c-myc, c-fos, c-Ki-ras, c-Ha-ras, and p53) was examined by Northern blot analysis using freshly isolated human colorectal and gastric cancers and noncancerous portions as the controls. Remarkably high levels of c-myc expression were found in colorectal cancers (eight of 11), but not in gastric cancers. High levels of c-myc expression were also detected in colorectal polyps and in metastatic liver tumors. In colorectal polyps, the transcript levels significantly correlated with the histologic malignancy and the size. In contrast, neither c-fos nor c-Ki-ras was overexpressed in colorectal and gastric cancers, and transcripts of c-Ha-ras and p53 were not evident in any tissue examined. In light of these observations the c-myc expression may be specifically associated with the evolution of colorectal cancer as well as progression and maintenance stages, hence may prove to be a useful marker to evaluate the malignant potential of colorectal polyps.
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PMID:Expression of c-myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential. 274 65

The possibility of an association between restriction fragment length polymorphisms (RFLPs) at the Ha-ras gene locus and susceptibility to develop colorectal cancer has been investigated. Leucocyte DNA from 46 carcinoma patients and 49 controls was analysed by Southern blotting to determine the size distribution of restriction fragments containing the variable tandem repeat 3' to the Ha-ras gene. Four predominant allelic fragments were found in both groups (in AvaII digests having sizes of 1.55, 2.0, 2.65 and 3.15 kilobases [kb]), together with a variety of 'rare' alleles (with individual frequencies less than 5%). The overall prevalence of rare alleles was not significantly different between cancer and control groups. The distribution of the common alleles, however, differed significantly. The combined frequency of the two larger alleles (a3 and a4) was approximately twice as high in the cancer group (34%) as in controls (18%) (P less than 0.025), which was reflected in a highly significant increase in the proportion of individuals carrying an a3 or a4 allele.
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PMID:Ha-ras restriction fragment length polymorphisms in colorectal cancer. 289 15

It has been well established that specific alterations in members of the ras gene family, H-ras, K-ras and N-ras, can convert them into active oncogenes. These alterations are either point mutations occurring in either codon 12, 13 or 61 or, alternatively, a 5- to 50-fold amplification of the wild-type gene. Activated ras oncogenes have been found in a significant proportion of all tumors but the incidence varies considerably with the tumor type: it is relatively frequent (20-40%) in colorectal cancer and acute myeloid leukemia, but absent or present only rarely in, for example, breast tumors and stomach cancer. No correlation has been found, yet, between the presence of absence of an activated ras gene and the clinical or biological features of the malignancy. The activation of ras oncogenes is only one step in the multistep process of tumor formation. The presence of mutated ras genes in benign polyps of the colon indicates that activation can be an early event, possibly even the initiating event. However, it can also occur later in the course of carcinogenesis to initiate for instance the transition of a benign polyp of the colon into a malignant carcinoma or to convert a primary melanoma into a metastatic tumor. Apparently, the activation of ras genes is not an obligatory event but when it occurs it can contribute to both early and advanced stages of human carcinogenesis.
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PMID:The ras gene family and human carcinogenesis. 328 42

Colorectal cancer is one of the most common malignancies in Norway. Many cases of the disease are detected at a stage where surgery is unlikely to result in cure. Currently used screening tests based on faecal occult blood and other tumour markers are poor indicators of colorectal neoplasia. Multiple gene alterations are associated with colorectal carcinogenesis. Mutations in the Ki-ras oncogene occur in 50% of colorectal carcinomas and also in 50% of the precursor lesions, the adenomas. These mutations have proved to be detectable in the faeces of patients with colorectal tumours, but the techniques used so far have been impractical for screening purposes. We have developed a rapid and simple laboratory technique, based on the polymerase chain reaction, for detecting mutated Ki-ras in the faeces. In eight of 12 patients with mutated Ki-ras in adenomas or carcinomas we found the corresponding mutations in stool samples. Our results represent a significant progression towards a simple and effective DNA-based screening strategy for early detection of curable colorectal cancer.
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PMID:[Determination of the activated proto-oncogene (Ki-ras) in feces. A new laboratory analysis for early diagnosis of colorectal cancer]. 748 56

Point mutations that activate the Ki-ras proto-oncogene are present in approximately 50% of human colorectal tumors and the activated Ki-ras gene is considered to play an important role in colorectal cancer cell proliferation. Five different colon cancer cell lines and two kinds of control cell lines were treated with antisense oligonucleotides complementary to the messenger RNA of Ki-ras. Treatment with antisense oligonucleotides at concentrations between 10 and 40 microM significantly and dose-dependently inhibited cell growth, colony formation and Ki-ras protein production of the colon cancer cells with activated Ki-ras, but did not affect the normal cells and colon cancer cells without Ki-ras mutation. These results show that use of synthetic oligonucleotides is an effective way of producing antisense-mediated changes in the behavior of human colon cancer cells with an activated Ki-ras gene.
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PMID:Inhibition of colon cancer cell proliferation by antisense oligonucleotides targeting the messenger RNA of the Ki-ras gene. 757 59

To elucidate the relationship between oncogene overexpression and malignant potential of colorectal cancer, the expression of three genes, c-myc, c-fos and c-Ki-ras was examined. Northern blot hybridisation was performed on fresh tissues excised from 35 patients with primary colorectal cancer. Overexpression of c-myc mRNA was evident in 25 of the patients (71%). Tumours with c-myc overexpression had a significantly higher frequency of lymph node metastasis than did those without (68 versus 20%, P < 0.05). The survival rate tended to be poorer (P = 0.06) in patients with c-myc overexpression (79% for 3 years) than in those without it (100%). We found no significant relationship between overexpression of the other two genes and pathological features. These findings suggest that c-myc overexpression is one parameter which can be used to determine the malignant potential of colorectal cancer.
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PMID:c-myc mRNA overexpression is associated with lymph node metastasis in colorectal cancer. 765 41

Ras oncogene and p53 gene mutations are frequently observed in colorectal cancers. The role of co-operation between these two genes in the tumorigenesis of colorectal cancer was evaluated. Point mutations in K-ras oncogene and hotspot codons of p53 gene of colorectal cancers were evaluated by naturally created or amplified created restriction site method. Nine of 42 cases (21.4%) of colorectal cancer showed K-ras oncogene mutations. Six of 42 cases (14.3%) of colorectal cancer showed p53 gene hotspot point mutations. The low frequency of p53 gene mutation in this series may be due to racial difference or different hotspot codons. When six cases with mutated p53 gene were examined, only one (16.7%) showed concurrent K-ras oncogene codon 12 and p53 gene codon 248 mutations. We concluded that the co-operation between ras oncogene and p53 gene hotspot point mutations in the tumorigenesis of colorectal cancer in Chinese was not common. Other factors such as adenomatous polyposis coli gene mutations, oncogene activation or tumour suppression gene inactivation may be involved.
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PMID:Ras oncogene and p53 gene hotspot mutations in colorectal cancers. 778 54

The series of genetic changes leading to malignancy in colorectal cancer is well reported. This includes mutational activation of the proto-oncogene Ki-ras and mutation/deletion of the p53 tumour suppressor gene. The frequency of these mutations was investigated in a panel of 52 colorectal cancer patients using a combination of immunocytochemistry and non-radioactive, digoxigenin-labelled in situ hybridisation. Sixty two per cent (32 of 52) of the study population were positive for p53 overexpression and 36% (19 of 52) positive for Ki-ras mutation. Twenty seven per cent (14 of 52) of the patients expressed both mutations. Mutation of either the p53 or the Ki-ras gene did not correlate with Dukes's stage, tumour differentiation or 5 year survival rate of the patients. Most of the rectal carcinoma specimens (11 of 15) showed p53 over-expression but the significance of this was not supported statistically. Thus detection of molecular changes is becoming more amenable to incorporation into routine histological carcinoma assessment because of the advent of non-radioactive labelling in in situ hybridisation and antibodies suitable for paraffin wax embedded specimens. The significance of these mutations in disease prognosis, however, remains questionable.
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PMID:Mutations of Ki-ras and p53 genes in colorectal cancer and their prognostic significance. 782 87


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