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S Olschwang

Publications and source records attributed to S Olschwang.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Genetic anomalies of colorectal cancers].

The prognosis of colorectal cancer has been based essentially on pathological data for many years. The analysis of genetic anomalies has led to fundamental progress and clinical advances. Genetic anomalies are routinely studied. 1--Flowcytometry evaluates the quantity of DNA in the nucleus during the cell cycle. 2--Cytogentics is the study of karyotype anomalies by loss or gain of chromosome material and structural changes. 3--Molecular biology gives a means of recognizing chromosome losses and especially to study oncogenic or antioncogenic mutations. These analyses allow: 1--an evaluation of their value as a prognosis factor and thus their use for indicating adjuvant medical and/or surgical treatments. 2--an understanding of cancerogenic processes. 3--the development of future therapeutic techniques based on a better understanding of the mechanisms involved. 4--familial counselling in high risk families and an examination of responsible or favouring genes in certain familial cancers. Research into familial forms has recently led led to the demonstration of genetic alterations located on chromosomes 1 and 2. These anomalies called RER correspond to alterations found on tumors. Studying these alterations will allow better prediction of high risk subjects in cancer families without polyposis.

Colorectal Neoplasms↗
PubMed1994

[Familial adenomatous polyposis].

Familial adenomatous polyposis is a rare genetic disease with a dominant mode of inheritance, involved in 1% of colorectal cancer. The APC gene, responsible for the disease, has been localized on the long arm of chromosome 5 and has recently been cloned and sequenced. Mutations predicted to alter the coding property of the APC gene have been reported in large series of adenomatous polyposis patients. Some of them have been correlated with an attenuated phenotype. A genetic test has been developed in affected families. Systematic screening of registered at-risk relatives has allowed a significant reduction of the median age at adenomatous polyposis diagnosis, and thus the incidence of colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed1994

[Contribution of genetic typing for the diagnosis of familial adenomatous polyposis in pediatrics].

BACKGROUND: The gene responsible for familial adenomatous polyposis, (APC), has been recently cloned and genetic map with several polymorphic markers has been established. POPULATION AND METHODS: Blood samples (20 ml) were taken from 34 subjects belonging to four families at risk for familial adenomatous polyposis. Nineteen of these 34, less than 20 years old, had one parent having polyposis or dead because of it. Polyposis was diagnosed, in ten of these 19 by endoscopy. Genomic DNA was extracted from peripheral leukocytes and Southern blot analyses were performed in each family, using RFLPs on both sides of the APC locus. RESULTS: DNA analysis identified normal and mutant haplotypes at the APC locus in each family. It was thus possible to follow the segregation of mutant alleles. These results were compared with the anamnestic and endoscopic data. Bearing in mind the risk of recombination when using extragenic markers, RFLPs allowed early diagnosis of APC in pre and/or asymptomatic patients. CONCLUSIONS: Genetic analysis can be used to diagnose APC in affected families, provided the risk of recombination is taken into account. Intragenic microsatellites markers will soon be available. These will provide more information on the APC gene, and hence direct molecular diagnosis of APC.

Adenomatous Polyposis Coli↗
PubMed1993

Alleles of the APC gene: an attenuated form of familial polyposis.

An attenuated form of familial adenomatous polyposis coli, AAPC, causes relatively few colonic polyps, but still carries a significant risk of colon cancer. The mutant alleles responsible for this attenuated phenotype have been mapped in several families to the adenomatous polyposis coli (APC) locus on human chromosome 5q. Four distinct mutations in the APC gene have now been identified in seven AAPC families. These mutations that predict truncation products, either by single base pair changes or frameshifts, are similar to mutations identified in families with classical APC. However, they differ in that the four mutated sites are located very close to one another and nearer the 5' end of the APC gene than any base substitutions or small deletions yet discovered in patients with classical APC.

Adenomatous Polyposis Coli↗
PubMed1993

Restriction of ocular fundus lesions to a specific subgroup of APC mutations in adenomatous polyposis coli patients.

In humans, alteration of the tumor suppressor gene, APC, causes adenomatous polyposis coli, a condition causing predisposition to colorectal cancer. The syndrome inconsistently associates characteristic patches of congenital hypertrophy of the retinal pigment epithelium (CHRPE). Ocular examination revealed that patients expressing CHRPE tend to cluster within specific families. The exact APC mutation was identified in 42 unrelated patients. In all cases these mutations were predicted to lead to the synthesis of a truncated protein. The extent of CHRPE was found to be dependent on the position of the mutation along the coding sequence. CHRPE lesions are almost always absent if the mutation occurs before exon 9, but are systematically present if it occurs after this exon. Thus, the range of phenotypic expression observed among affected patients may result in part from different allelic manifestations of APC mutations.

Adenomatous Polyposis Coli↗
PubMed1993

Is the multiple endocrine neoplasia type 1 gene a suppressor for fundic argyrophil tumors in the Zollinger-Ellison syndrome?

In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors have been described only in the small genetically defined subgroup of patients who have the multiple endocrine neoplasia type 1 syndrome (MEN-1). Allelic losses on 11q13, on which MEN-1 gene has been localized, have been noted in parathyroid and pancreatic tumors of patients with MEN-1, suggesting that the MEN-1 gene could act as a recessive tumor suppressor gene. One fundic argyrophil carcinoid tumor from a patient with the Zollinger-Ellison syndrome and MEN-1 was studied. Loss of heterozygosity in the tumor DNA at loci close to MEN-1 locus was looked for using Southern technique with six DNA probes. Segregation of alleles was examined in relatives. In the tumor DNA, we found the loss of one allele with PYGM, the closest probe to the MEN-1 locus. The allele lost in the tumor had been transmitted by the unaffected parent. This suggests that in patients with the Zollinger-Ellison syndrome and MEN-1, the promotion of fundic argyrophil carcinoid tumors results from the inactivation of the two copies of MEN-1 gene and that fundic argyrophil carcinoid tumors may be included in the spectrum of MEN-1-related tumors.

Adult↗
PubMed1993

[Presymptomatic detection of familial colonic polyposis].

In familial adenomatous polyposis coli (APC) it is possible to detect APC carriers either by research of bilateral congenital hypertrophy of the retinal pigment epithelium (CHRPE) or by genetic diagnosis (APC gene is localized in 5q21). These detections were performed in 33 patients of four families with the same positivity for genetic typing (11 patients) or for CHRPE (11 patients) which thus avoided annual coloscopy.

Adenomatous Polyposis Coli↗
PubMed1993

[Genetic heterogeneity of certain sporadic colorectal cancers].

Intratumoral heterogeneity provides information concerning the timing of genetic events which occur during colorectal carcinogenesis. In a series of 14 colorectal adenocarcinomas, the following genetic alterations were characterized: loss of heterozygosity on chromosomes 17 p, 1 p, 18 q, 5 q and 22 q, point mutations on TP53 and K-RAS genes, change in DNA index. Six of the 14 initial samples were investigated for putative genetic heterogeneity. In two cases, variations in genetic alterations on chromosome 17 p and gene TP53 were demonstrated. These events seem to occur at a late stage in colorectal carcinogenesis.

Adenocarcinoma↗
PubMed1993

Germ-line mutations in the first 14 exons of the adenomatous polyposis coli (APC) gene.

The first 14 exons of the APC gene have been screened by the denaturation gradient gel electrophoresis method in 160 unrelated patients with familial adenomatous polyposis coli (APC) syndrome. Four polymorphic variants corresponding to silent mutations not associated with the disease phenotype were observed. Mutations predicted to alter the coding property of the APC gene were observed in 26 patients. All these mutations are expected to lead either to aberrant splicing, to synthesis of a truncated APC protein because of the emergence of a stop codon, or to a change in the translation reading frame. Single-base-pair substitutions were observed on 21 occasions. The most frequent mutation (eight cases) was a C-to-T change which exclusively occurred on the nontranscribed strand within a CG dinucleotide.

Adenomatous Polyposis Coli↗
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↗