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S Olschwang

Publications and source records attributed to S Olschwang.

At least 19 recordsLinked to original sources
PubMed1992

Detection by DGGE of a new polymorphism closely linked to the adenomatous polyposis coli region.

The EF5.44 locus is in close proximity to the chromosome 5 region to which the genetic defect responsible for familial adenomatous polyposis has been mapped. We have devised two oligonucleotides that promote the specific polymerase chain reaction (PCR) amplification of a 365-bp sequence in this region. Analysis by denaturing gradient gel electrophoresis of the resulting fragment has unravelled individual differences that could be identified as a single base pair change in a MnlI restriction site. This PCR assayable polymorphism increases the informativeness at this locus, and should be useful in the presymptomatic diagnosis of familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1992

[Familial adenomatous polyposis: early diagnosis by genetic mapping].

The use of probes detecting polymorphic loci within the human population has enabled accurate localization of the genetic defect responsible for familial adenomatous polyposis on chromosome 5. This was used to screen two families for the presymptomatic diagnosis in children of an affected parent. In both cases, the use of 8 polymorphic probes located on either side of the gene provided information which could be used in the management of children born from the patients at risk. The set of probes used in this work should be informative in most of the affected adenomatous polyposis families.

Adenomatous Polyposis Coli↗
PubMed1992

[Value of screening of familial adenomatous polyposis for the prevention of colorectal cancer].

Familial adenomatous polyposis coli is a hereditary autosomal dominant disease which spontaneously and inevitably leads to degeneration of colorectal adenomas and requires preventive surgical treatment. The aim of this study was to evaluate the age of colorectal degeneration and the need for a screening technique in family members. Between 1983 and 1989, 141 patients were treated for familial adenomatous polyposis in our surgical center. Mean age at surgery was 32 years and 64 patients (45.4 percent) had a colorectal carcinoma. Thirty had an in situ tumor (mean age: 30 years) and 34 had an invasive adenocarcinoma (mean age: 45 years), 7 of whom died of their cancer. No colonic cancer was found in patients younger than 20. Thirty-eight percent of the patients under 40 years of age, 73 percent of the patients older than 40 years and 81 percent of those older than 50 had an adenocarcinoma. Fifty percent of the patients with carcinoma were younger than 40 years and 7 percent were less than 25 years old. Seventy-one patients were symptomatic at the time of operation (mean age: 40 years), 32 (45 percent) had a colonic cancer. In 70 patients, familial adenomatous polyposis was detected by screening (mean age: 24) and 2.8 percent had a colonic carcinoma. We conclude that the age-related risk of developing colonic carcinoma requires prophylactic surgery in asymptomatic patients before 20 years of age, and that routine familial screening would be of some benefit.

Adenocarcinoma↗
PubMed1992

Survival and acquired genetic alterations in colorectal cancer.

To set the basis for a precise assessment of new therapeutic approaches, the prognosis of patients with colorectal cancer should be evaluated with the highest precision. The recent discovery, in tumor cells, of somatically acquired genetic alterations believed to be instrumental in tumor behavior may provide new independent prognostic factors. In the present study, the usual prognostic factors and a set of genetic alterations, i.e., Ki-ras mutations, DNA content, and allelic losses on chromosome 17p, 18q, 5q, and 1p, were investigated in 109 colorectal carcinomas. Univariate analysis for correlation with 5-year survival showed the following significant associations: histological staging (P less than 0.00001), preoperative serum carcinoembryonic antigen concentration (P less than 0.002), DNA content (P less than 0.009), and allelic loss on the short arm of chromosome 17 (P less than 0.002) and 1 (P less than 0.03). In multivariate analysis, only histological staging and allelic loss on the short arm of chromosome 17 were found to be independently associated with shorter survival (P less than 0.0001 and P less than 0.004, respectively). Loss of 17p alleles in colorectal carcinoma thus appears to be a marker of tumor aggressiveness. Its monitoring may lead to an improved classification of patients when adjuvant chemotherapy is considered.

Aged↗
PubMed1991

Association of Ki-ras mutation with differentiation and tumor-formation pathways in colorectal carcinoma.

The occurrence of a point mutation on the 12th and 13th codons of the Ki-ras oncogene has been investigated in 99 colorectal carcinomas in relation to 3 histological parameters: extent of differentiation, occurrence of a mucinous component within the tumor, and presence of peripheral adenomatous polyp remnants. The mutation frequency increased with each parameter: from 13% (2/15) to 44% (37/84) with differentiation, from 33% (26/79) to 65% (13/20) with mucinous character, and from 27% (15/56) to 56% (24/43) with the presence of polyp remnants. The frequency was highest in well-differentiated mucinous tumors with adenomatous remnants 83% (5/6). We suggest that Ki-ras mutation is preferentially involved in carcinomas that have developed from adenoma and that the mutation preserves differentiation and mucin secretion in these cancer cells.

Adenocarcinoma, Mucinous↗
PubMed1991

Genetic characterization of the APC locus involved in familial adenomatous polyposis.

Familial adenomatous polyposis is a rare disease inherited in a Mendelian dominant fashion. It is characterized by the occurrence of more than 100 adenomatous polyps in the large bowels of affected individuals. The genetic defect responsible for adenomatous polyposis resides at a locus called APC which has been localized to the long arm of human chromosome 5. In this study, the APC locus was mapped with respect to 11 markers known to map to this chromosomal segment. Linkage of APC to four of these markers had been previously reported. Three additional markers are shown here to be linked to APC. By multipoint analysis, the APC locus maps to an interval bounded by D5S49 and D5S58. The refined map of the APC locus and the new markers described here improve the informativeness and accuracy of the presymptomatic diagnosis of familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1990

Cytogenetic and molecular approaches of polyploidization in colorectal adenocarcinomas.

We present the cytogenetic analysis of 23 cases of polyploid colorectal adenocarcinomas. We took advantage of the high intratumoral heterogeneity of the karyotypes to identify clones, subclones, and cell-to-cell variations. This allowed us to reconstruct the chromosomal evolution of each tumor and to propose a schema of the chromosomal changes in relation to the endoreduplication process. All but one case were characterized by a relative deficiency of chromosomes 17p and 18. Other deficiencies affecting the late-replicating X, and to a lesser degree, 1p, 5q, 14, 15, 8p, 10, 21, and 4, and excesses affecting the early-replicating X, 8q, 13, 16, 17q, and 11 were frequently associated. This pattern of imbalances is very similar to that of the monosomic type previously described in near-diploid tumors. The pattern of the 23rd tumor corresponded to those of the trisomic type tumors. These data largely confirm the existence of two distinct processes of chromosomal evolution in colorectal adenocarcinomas, with a strong tendency to undergo endoreduplication for the monosomic type near-diploid tumors. To correlate cytogenetic and molecular data, allelic losses analyses were investigated for probes of chromosomes 17p and 18. In all 12 informative tumors, a loss of heterozygosity for probes of the short arm of chromosome 17 indicated the occurrence of a rearrangement of chromosome 17 before the endoreduplication. The same was true for allelic losses for probes of chromosome 18 found in 11 of 12 informative tumors. The correlation between cytogenetic and molecular data is thus excellent and indicates that losses of 17p and 18 are early events in the tumor process.

Adenocarcinoma↗
PubMed1990

[A joint study of mutation of the Ki-ras oncogene and overexpression of the Tp53 oncogene in colorectal cancer].

Twenty-five colorectal tumors (rectum 6, left colon 13, right colon 6) were studied with respect to the overexpression of p53 and the activation by point mutation of the Ki-ras oncogene. Single point mutations on codon 12 and codon 13 were analyzed after PCR amplivication, dotblotting and sequential hybridization with 12 different oligonucleotides. The intranuclear concentration of p53 protein was measured by flow cytometry after immunofluorescence staining with monoclonal antibody Pab 421. Twelve tumors were found to significantly overexpress p53 and 6 of them had an activated Ki-ras (5 on codon 12, 1 on codon 13). Of 13 tumors which failed to demonstrate over expression of p53, 8 had an activated Ki-ras (5 on codon 12, 3 on codon 13). In our series, p53 overexpression and ki-ras activation appeared to be independent.

Adenocarcinoma↗
PubMed1989

Preservation of chromosome and DNA characteristics of human colorectal adenocarcinomas after passage in nude mice.

Twenty-seven human colorectal adenocarcinomas were implanted s.c. into nude mice. A comparative study of chromosomes and DNA between fresh tumor (FT) and xenografted tumor cells (XT) could be performed in 9 cases. Losses or deletions were consistently found in FTs as well as in XTs, particularly on chromosomes 17 and/or 18. This was correlated with loss of heterozygosity for these chromosomes. Comparison between corresponding FT and XT karyotypes showed great similarities. However, the tendency toward polyploidization, which exists in FTs, appeared to be more pronounced in XTs. Passage in nude mice makes it possible to repeat cytogenetic analyses in order to obtained interpretable metaphases. Xenografting not only increases the number of tumorigenic cells, but also eliminates human normal stromal or blood cells and gives unambiguous data on allelic loss.

Adenocarcinoma↗
PubMed1989

Multiple genetic alterations in distal and proximal colorectal cancer.

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.

Adenocarcinoma↗
PubMed1988

Concerted nonsyntenic allelic loss in human colorectal carcinoma.

Familial polyposis coli (FPC) is caused by an autosomal dominant gene on chromosome 5, and it has been proposed that colorectal cancer in the general population arises from loss or inactivation of the FPC gene, analogous to recessive tumor genes in retinoblastoma and Wilms' tumor. Since allelic loss can be erroneously scored in nonhomogeneous samples, tumor cell populations were first microdissected from 24 colorectal carcinomas, an additional nine cancers were engrafted in nude mice, and nuclei were flow-sorted from an additional two. Of 31 cancers informative for chromosome 5 markers, only 6 (19%) showed loss of heterozygosity of chromosome 5 alleles, compared to 19 of 34 (56%) on chromosome 17, and 17 of 33 (52%) on chromosome 18. Therefore, it appears that (i) FPC is a true dominant for adenomatosis but not a common recessive gene for colon cancer; and (ii) simple Mendelian models involving loss of alleles at a single locus may be inappropriate for understanding common human solid tumors.

Adenocarcinoma↗
PubMed1988

Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12).

Since our initial reports on chromosomal studies in eight Ewing's sarcomas (ES), we have carried out similar investigations on 23 additional ES specimens following short-term culture of tumor cells (16 cases), and established in vitro cell lines (three cases) and on xenografted tumors in nude mice (four cases). We demonstrated the presence of the reciprocal t(11;22)(q24;q12) in every case except one that exhibited a complex t(11;22;14)(q24;q12;q11). On the basis of results from these additional 23 cases, we confirm the consistency of the t(11;22)(q24;q12) in ES. Moreover, we reviewed 54 ES cases reported by other investigators; when added to our 31 cases, this brings the total number to 85 unrelated cases of ES available for an evaluation of the frequency of involvement of bands 11q24 and 22q12 in translocations in ES. The standard t(11;22)(q24;q12) proved to be a remarkably consistent event, present in 83% of the cases. Five percent of the cases exhibited complex translocations involving a third chromosome in addition to chromosomes #11 and #22. In 4% of the cases variant translocations involved 22q12 but with a chromosome(s) other than #11. The breakpoint on chromosome 22q12 appears to be the most consistently observed event in 92% of the cases, whereas, the breakpoint at chromosome 11q24 was observed in 88% of the cases.

Adolescent↗