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L Catasus

Publications and source records attributed to L Catasus.

8 recordsLinked to original sources
PubMed2001

Microsatellite instability, MLH-1 promoter hypermethylation, and frameshift mutations at coding mononucleotide repeat microsatellites in ovarian tumors.

BACKGROUND: Microsatellite instability (MI) is frequent in endometrial carcinomas (ECs), but its occurrence in ovarian tumors is uncertain. Microsatellite instability positive ECs frequently are associated with frameshift mutations in coding mononucleotide tracts in IGFIIR, BAX, hMSH6, and hMSH3. METHODS: DNA from 52 consecutive patients with ovarian tumors (10 benign, 7 borderline, and 35 malignant) was obtained from neoplastic and normal tissue. After preliminary results, the series was expanded by including 41 additional, previously selected, endometrioid and clear cell carcinomas. Microsatellite instability analysis was assessed by evaluating three (CA)n dinucleotide repeats (D2S123, D5S346, D17S250) and two mononucleotide tracts (BAT 25 and BAT 26). Frameshift mutations at coding mononucleotide repeats (IGFIIR, TGF beta II, BAX, hMSH6, and hMSH3) were investigated by single-strand conformation polymorphism analysis and DNA sequencing. MLH-1 methylation was assessed by methylation specific PCR. RESULTS: Microsatellite instability was identified in only 2 of the 52 (3.8%) tumors of the initial series (1 endometrioid and 1 clear cell carcinoma). After expanding the initial series of 15 endometrioid and clear cell carcinomas with 41 additional endometrioid and clear cell carcinomas, MI was found in 7 of the total series of 56 endometrioid and clear cell carcinomas (12.5%). Frameshift mutations in coding mononucleotide tracts were detected in BAX (6 of 7), IGFIIR (1 of 7), and MSH3 (2 of 7). MLH-1 promoter hypermethylation was identified in three of six MI positive tumors. CONCLUSIONS: Microsatellite instability was infrequent in this series of ovarian tumors, and it was limited to endometrioid and clear cell carcinomas. Like EC, many ovarian carcinomas with MI follow the same process of MLH-1 promoter methylation and accumulation of mutations in coding mononucleotide tracts.

Adaptor Proteins, Signal Transducing↗
PubMed2001

K-ras mutations in endometrial carcinomas with microsatellite instability.

K-ras mutations are known to occur in hyperplasias and carcinomas of the endometrium. No clear correlation has been found yet between K-ras mutations and microsatellite instability (MI) in these lesions. Fifty-eight endometrial carcinomas (ECs) and 22 endometrial hyperplasias (EHs) were analysed for K-ras mutation by single-strand conformational polymorphism analysis (SSCP), restriction analysis, and DNA sequencing. MI status had been established previously at five dinucleotide loci and was reconfirmed with markers BAT-25 and BAT-26 by SSCP. K-ras mutations were detected in 11 ECs (18.9%). All 11 tumours were endometrioid carcinomas. K-ras mutations were more frequent in MI-positive (6/14, 42.8%) than in MI-negative tumours (5/44, 11.3%) (p=0.017). Methylation-related transitions were detected in five of the six MI-positive tumours but in only one of the five MI-negative carcinomas. K-ras mutation was identified in only one atypical EH (1/22, 4.5%); in this case, the EH co-existed with EC and both lesions exhibited MI. The results support a close relationship between K-ras mutations and the phenomenon of MI in endometrial carcinomas. The frequent occurrence of methylation-related transitions in these tumours may indicate a cause-effect relationship with the altered methylation status which has been described in association with MI.

Carcinoma↗
PubMed2001

Molecular pathology of endometrial hyperplasia and carcinoma.

Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.

Cytoskeletal Proteins↗
PubMed2000

Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability.

BACKGROUND: Microsatellite instability (MI) is a frequent occurrence in endometrioid carcinoma of the endometrium (EC). Several genes known to contain mononucleotide short tracts in their coding sequences (TGF-beta RII, IGFIIR, BAX, hMSH6, and hMSH3) are likely targets for mutations in these tumors. METHODS: DNA from 24 patients with EC and MI was extracted from blood and from fresh-frozen and paraffin embedded tumor tissue. Seven of these patients were found to have metastatic spread to paraaortic lymph nodes. DNA also was studied from 10 patients with EC without MI. RESULTS: Frameshift mutations at coding mononucleotide repeats were detected by single strand conformation polymorphism analysis and DNA sequencing. Frameshift mutations were detected more frequently in BAX (11 of 24 MI positive (+) tumors; 45.8%) than in TGF-beta RII (0 of 24 tumors; 0%), IGFIIR (3 of 24 tumors; 12.5%), hMSH3 (6 of 24 tumors; 25%), or hMSH6 (0 of 24 tumors; 0%). The mutations frequently were distributed heterogeneously throughout the tumors. Overall, frameshift mutations at 1 or more of these mononucleotide repeat microsatellites were found in 17 of 24 MI+ tumors (70.8%) but in none of the 10 MI negative neoplasms. In the seven EC patients with lymph node metastases, mutations in IGFRII were found more commonly in those with metastatic (three of seven patients) rather than primary (one of seven) tumors. CONCLUSIONS: The results of the current study confirm that BAX is an important target gene in ECs with MI. The frequent detection of IGFRII frameshift mutations in lymph node metastases suggest that IGFRII may play a role in tumor progression in these patients.

Endometrial Neoplasms↗
PubMed1999

hMLH1 promoter hypermethylation is an early event in human endometrial tumorigenesis.

It has recently been suggested that silencing of the hMLH1 gene by promoter hypermethylation is the mechanism underlying the presence of the microsatellite instability (MSI) phenotype in sporadic colon and endometrial carcinomas. To determine whether hMLH1 promoter hypermethylation is a relatively early event in endometrial tumorigenesis we evaluated endometrial hyperplasia (EH) characterized as simple, complex, and atypical (the direct precursor of endometrial carcinoma) for hMLH1 aberrant methylation. In addition, we studied the hMLH1, hMSH2, hMSH3, and hMSH6 promoter methylation and MSI status of those endometrial carcinomas with synchronous hyperplasias and those without them. We found that 11 of 12 (91%) cases of endometrial carcinoma (EC) displaying MSI had hMLH1 promoter hypermethylation, whereas aberrant methylation of any of the other mismatch repair genes was not observed. All 15 cases of EC without MSI were unmethylated at hMLH1. Abnormal methylation of hMLH1 was also present in 8 of 116 (7%) cases of EH and was restricted primarily to the atypical endometrial hyperplasia (AEH) type with coexisting endometrial carcinoma. In this set, half of EH methylated at hMLH1 displayed MSI, whereas none of the unmethylated EH had MSI. Our data suggest that hypermethylation of hMLH1 can be an early event in the pathogenesis of EC, preceding the development of an apparent MSI phenotype in a subset of cases.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Microsatellite instability in endometrial carcinomas: clinicopathologic correlations in a series of 42 cases.

Instability at microsatellite repeat sequences (MI) has been observed in endometrial carcinomas (EC) arising sporadically or in association with the hereditary colon cancer syndrome. However, the clinical and pathological features of the EC with MI have not been characterized. DNA of 42 patients with EC was extracted from blood and from fresh-frozen and paraffin-embedded tumor tissue. Microsatellite loci on chromosomes 4, 5, 10, 12, 17, and 18 were amplified by polymerase chain reaction. MI was defined by a mobility shift in the tumor DNA as compared with normal DNA. Results were correlated with the clinical and pathological features of the tumors. MI at three or more loci was detected in 12 of 42 cases (28%). There were no significant differences between EC with and without MI with regard to age of presentation, stage, evidence of estrogenic stimulation, mucinous differentiation, estrogen receptor, c-erbB2, or p53 immunostaining. However, MI was more frequent in endometrioid (11/33, 33.3%) than in nonendometrioid (1/9, 11%) carcinomas. Only one papillary serous carcinomas showed MI. MI was found in one of two cases of endometrial hyperplasia adjacent to EC. It was concluded that MI is a common genetic abnormality of endometrial carcinoma and appears to be more frequent in endometrioid than in nonendometrioid tumors.

Adult↗