Biomedical subjects

G Sourvinos

Publications and source records attributed to G Sourvinos.

At least 37 records · Page 2Linked to original sources

PubMed1999

Low incidence of H-, K- and N-ras oncogene mutations in cytological specimens of laryngeal tumours.

Laryngeal cancer is a rare type of neoplasia, constituting approximately 2% of all human cancers. Mutations of the ras gene family is one of the main activating mechanisms in human cancer. Their involvement in head and neck cancer has been mainly demonstrated at the level of the overexpression whereas ras mutations in these cancers are rare in the Western world. In the present study we explored the incidence of codon 12-point mutation in the H-, K- and N-ras genes, in 41 laryngeal cytological specimens. These specimens corresponded to 19 benign and 22 malignant lesions of the larynx. Only two specimens carried a codon 12-point mutation in the K-ras gene (4.8%) while no mutation was detected in the H- and N-ras genes. K-ras mutations were detected in one benign and one malignant specimen. These results indicate low incidence of ras oncogene mutations in laryngeal cytological specimens.

Carcinoma, Squamous Cell↗

PubMed1999

Detection and clinical correlations of ras gene mutations in human ovarian tumors.

In epithelial ovarian neoplasms K-ras codon 12 gene mutations show a wide variation fluctuating between 4-39% in invasive carcinomas and 20-48% in borderline malignant tumors. In this study, we showed the pattern of point mutations in codon 12 of the K-ras, H-ras and N-ras genes, using polymerase chain reaction restriction fragment length polymorphism analysis in 74 tissue specimens of Greek patients with epithelial ovarian tumors. K-ras and H-ras gene mutations were detected in 11/48 (23%) and 3/48 (6%) cases with primary invasive ovarian carcinomas, respectively, while N-ras gene mutations were not found. No mutation of K-, H- and N-ras genes was detected in 23 ovarian cystadenomas. In 1 out of 3 borderline ovarian tumors (33%) we found an H-ras gene mutation. The prevalence of mutations in K-ras gene was 1/8 (13%) in mucinous, 7/29 (24%) in serous, 1/3 (33%) in endometrioid and 2/8 (25%) in clear-cell adenocarcinomas and in H-ras gene 1/8 (13%) in mucinous and 2/29 (7%) in serous adenocarcinomas. Analysis of the results revealed no significant correlation between ras gene mutations and clinicopathological parameters or clinical outcome of this primary invasive ovarian carcinoma population. Our present data suggest that ras gene mutations in invasive ovarian carcinomas occur in 29% of Greek patients and are not associated with the differentiation of the epithelial cells or the response of patients to adjuvant platinum-based chemotherapy.

Adenocarcinoma↗

PubMed1999

Microsatellite DNA instability and loss of heterozygosity in pulmonary sarcoidosis.

In the present study we investigated the incidence of microsatellite instability (MI) and loss of heterozygosity (LOH) in sarcoidosis, a multisystem disease of unknown origin. We examined sputum cytological specimens from 30 patients with sarcoidosis and 30 healthy, matched subjects, using 10 highly polymorphic microsatellite markers located at several chromosomal arms. The electrophoretic pattern of each specimen was compared with the corresponding pattern of peripheral blood and any difference in the mobility of the microsatellite alleles was interpreted as MI-positive. LOH was scored as decrease in intensity of one allele relative to the other as determined from comparison of sputum and normal (blood) DNA. We found that 14 (47%) sarcoidosis patients showed genetic alterations, either MI or LOH. Six (20%) patients exhibited MI and nine (30%) exhibited LOH in at least one microsatellite marker. One of the patients exhibited MI in two microsatellite markers and three (10%) showed LOH in more than one marker. One patient showed complete deletion of the chromosomal arm 17q11.2-q21. None of the healthy subjects exhibited any genetic alteration in the studied markers. No correlation was found between the genetic alterations detected and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that MI is a detectable phenomenon in sarcoidosis and seems not to be related with the severity of the disease. The detection of LOH indicates the presence of putative tumor suppressor genes at loci examined, which may play an important role in the etiopathogenesis of sarcoidosis.

Adult↗

PubMed1999

Microsatellite DNA instability in COPD.

STUDY OBJECTIVES: Cigarette smoking is the prime cause of COPD; however, only a few smokers develop the disease. In a previous study, we demonstrated that microsatellite DNA instability (MSI) is a detectable phenomenon in sputum cells of COPD patients. Therefore, we hypothesize that this genetic alteration may indicate susceptibility to COPD. DESIGN: In order to investigate this hypothesis, we compared smokers who developed COPD with smokers who did not develop COPD (referred to as non-COPD smokers). SETTING: Seven highly polymorphic microsatellite markers were targeted on the DNA of sputum cells and of WBCs. PATIENTS AND PARTICIPANTS: We studied 60 non-COPD smokers and 59 severe COPD patients with a similar smoking history (mean +/- SD) of 48+/-25 and 54+/-33 pack-years, respectively (p = 0.77). Non-COPD smokers were tested once; COPD smokers were tested twice, with an interval of 24 months between tests. RESULTS: MSI was detected in 14 COPD patients (24%) but in none of the non-COPD smokers. In 10 COPD patients, MSI was exhibited by one microsatellite marker; in the remaining 4 COPD patients, MSI was exhibited by two different alleles. The most commonly affected marker was THRA1 on chromosome 17 (43%). No significant differences were found between MSI-positive and MSI-negative COPD patients for clinical or laboratory parameters, survival, and development of lung cancer. No change in the microsatellite alleles was found between the tests performed with a 24-month interval. CONCLUSIONS: This study demonstrated that MSI was found exclusively in the sputum cells of smokers with COPD. The results support the hypothesis that MSI could be part of the complex genetic basis of COPD, and it could be a marker of the genetic alteration caused by smoking that allows COPD to develop.

Case-Control Studies↗

PubMed1999

Loss of heterozygosity in pseudoexfoliation syndrome.

PURPOSE: Pseudoexfoliation (PEX) syndrome is characterized by the accumulation of a material of unknown origin in the anterior structures of the eye. Loss of heterozygosity (LOH) in a genetic locus indicates the presence of a gene located in the same region that could be implicated in the development or the progression of a disease. In this study, the occurrence of LOH in tissues involved in PEX and the possible correlation of LOH incidence with clinical parameters were evaluated. METHODS: Twelve iris specimens, 12 anterior capsule specimens, and respective blood samples were obtained from 17 patients with PEX (13 men), who were undergoing glaucoma and cataract surgery. Sixteen anterior capsule specimens and four iris specimens were obtained from 16 patients without PEX. Polymerase chain reaction was used to amplify 10 highly polymorphic microsatellite markers located on chromosomes 1, 7, 9, and 13. RESULTS: Overall, 83.3% (20/24) of PEX specimens and 94.11% (16/17) of patients with PEX had LOH. The highest incidence of LOH was observed in marker D13S175 (41.6%) followed by D7S478 and D7S479 (37.5%). Only three non-PEX specimens displayed LOH. The number of loci lost was directly related to the altitude of the patients' present residence, but the number lost did not differ significantly between the iris and capsule samples. CONCLUSIONS: The occurrence of LOH in tissues involved in PEX implies a genetic role in PEX pathogenesis at a cellu lar level. The correlation of LOH incidence with the altitude of the patient's residence, could indicate an increased susceptibility to UV radiation of the chromosomal regions examined.

Aged↗

PubMed1998

Differential expression and mutation of the ras family genes in human breast cancer.

The expression of ras mRNA levels in 27 human sporadic breast cancer specimens was examined, and compared to the corresponding adjacent normal tissue using the RT-PCR technique. Eighteen out of the 27 specimens (67%) exhibited two- to four-fold increased expression of ras mRNA levels, compared to corresponding normal tissue. The rates of augmented mRNA expression were similar among the three ras genes. A statistically significant correlation of overexpression of ras genes in specimens classified as Stage I disease was observed, compared to tumors in a more advanced stage (II or III). The incidence of codon 12 point mutations of the K-ras gene in fresh tissue samples was also assessed in 61 human sporadic breast cancer cases. Point mutations were detected in four (6.5%) out of the 61 cases examined; no correlation was found with any clinicopathological parameter. This is the first report to our knowledge of the differential expression of the ras family genes in breast carcinoma. Our findings indicate that the aberrant expression of ras genes may be an initial event in breast cancer oncogenesis and that K-ras point mutations are rarely involved in the development of mammary neoplasias.

Breast Neoplasms↗

PubMed1998

Decreased BRCA1 expression levels may arrest the cell cycle through activation of p53 checkpoint in human sporadic breast tumors.

Predisposition to breast cancer has been attributed to mutant BRCA1 alleles whereas no BRCA1 mutation has been described yet in sporadic breast tumours. As an initial characterization of the regulation and function of the BRCA1 gene in sporadic breast cancer, we have compared the expression of BRCA1 in thirty-five paired tumour specimens versus their corresponding adjacent normal tissue. We found two- to five-fold reduced BRCA1 expression levels in tumour specimens as compared to normal tissue. Decreased BRCA1 expression was significantly associated with loss of heterozygosity (LOH) at the BRCA1 region, as well as with negative estrogen receptor (ER) status. Our results offer an alternative explanation of how BRCA1 could play an important role in sporadic breast cancer, not via mutations in coding sequences but due to transcriptional disregulation. Decreased BRCA1 mRNA may be caused due to loss of gene copies, deletions of regulatory elements in the BRCA1 promoter or failure of transcriptional regulation by estrogen receptors. We also investigated possible relationships between BRCA1, p53, mdm-2 and p21(WAF1/CIP1) at the expression level. p53 expression was unaffected in almost all the specimens, mdm-2 was overexpressed in 18/35 specimens while 21/35 overexpressed p21. Samples exhibiting reduced BRCA1 levels simultaneously overexpressed both p21 and mdm-2, showing that BRCA1, at certain levels, even reduced up to 2.7-fold, is functional and sufficient to upregulate p21, when p53 activity is inhibited by its negative regulator, the mdm-2. On the contrary, specimens exhibiting more than 2.7-fold reduced BRCA1 levels, overexpressed p21 while mdm-2 expression was normal, allowing us to speculate that p21 transcriptional activation is due to p53 activity, in cases with dramatically decreased BRCA1 expression. Our findings provide evidence, indicating that BRCA1 might affect cell cycle regulation and loss of BRCA1 function due to decreased expression leads to cell cycle arrest, through p53 and p21 genes.

BRCA1 Protein↗

PubMed1998

Microsatellite mutations in spontaneously aborted embryos.

OBJECTIVE: To evaluate the incidence of microsatellite instability in spontaneously aborted embryos. DESIGN: Retrospective study. SETTING: Laboratory of Clinical Virology and Department of Obstetrics and Gynecology, University Hospital, Medical School, University of Crete. PATIENT(S): Thirty-five women in whom spontaneous abortions occurred between the 6th and 20th weeks of pregnancy. INTERVENTION(S): Thirty-five aborted embryonic tissues were analyzed with seven microsatellite markers, and their haplotypes were compared with the corresponding pattern of their parents. MAIN OUTCOME MEASURE(S): Microsatellite DNA. RESULT(S): Microsatellite instability was observed in 8 of 35 cases (23%). In 7 of 8 positive cases, microsatellite instability was restricted to one of the seven microsatellite markers, whereas in one case, three microsatellite markers were affected by instability. A statistically significant association was found between microsatellite instability and a previous normal childbirth. CONCLUSION(S): Genetic instability is a detectable phenomenon in spontaneous abortions, representing a significant increase in the mutational rate of the embryo and providing evidence for a mechanism associated with the phenomenon of spontaneous abortion. We conclude that this elevated mutational rate affects active genomic sequences that play a critical role in the viability of the embryo, leading to cell death and abortion.

Abortion, Spontaneous↗

PubMed1998

Evaluation of Parvo B19, CMV and HPV viruses in human aborted material using the polymerase chain reaction technique.

OBJECTIVE: To investigate the role of human parvovirus B19 (Parvo B19), cytomegalovirus (CMV) and human papilloma virus (HPV) viruses in the aetiopathogenesis of spontaneous abortions. STUDY DESIGN: Abortion material from 102 cases of women with spontaneous abortions were analysed for the presence of Parvo B19, CMV and HPV DNA using the polymerase chain reaction (PCR) technique. Serological assays were used for the detection of specific IgM and IgG antibodies against Parvo B19 virus and CMV in the maternal sera. RESULTS: Parvo B19 virus genome was detected in two cases of spontaneous abortion, by PCR amplification, while CMV and HPV genomes were not observed. Serological markers were indicative for Parvo B19 virus and CMV infection in ten and four cases, respectively. CONCLUSIONS: PCR is a useful method for investigating the viral contribution to the aetiopathogenesis of spontaneous abortions and for detecting the viral genome in the abortion material. This study of 102 cases of spontaneous abortion does not implicate CMV and HPV in the aetiopathogenesis of spontaneous abortion, although it indicates a possible abortional role for Parvo B19 virus.

Abortion, Spontaneous↗

PubMed1998

Loss of heterozygosity at 8p, 9p and 17q in laryngeal cytological specimens.

The activation of oncogenes and the inactivation of tumour suppressor genes play a critical role in laryngeal tumorigenesis. Recent investigations revealed that 8p, 9p and 17q arms of human chromosomes harbour tumour suppressor genes (TSGs) such as p16 and BRCA1 with an important role in the multistage carcinogenesis of the larynx. In order to investigate the implication of these novel TSGs in the development of laryngeal neoplasia we performed a loss of heterozygosity (LOH) analysis using a bank of 15 polymorphic microsatellite markers (4 at 8p21, 7 at 9p21 arm and 4 at 17q arm surrounding the BRCA1 region) in a series of 32 cytological specimens (19 squamous cell carcinoma, 13 benign lesions of the larynx). Both benign and malignant specimens exhibited genetic alterations with at least one microsatellite marker. Fifteen (47%) out of the 32 specimens exhibited LOH at 8p21, 25/32 (78%) showed LOH at 9p21 and 18/32 (56%) displayed LOH at 17q21. Genetic alterations were detected in both benign and malignant lesions for all the loci tested suggesting an important role of these regions in the development of laryngeal neoplasia. This is the first report of detection of microsatellite alterations not only in solid tumours of the larynx but in laryngeal cytological specimens, suggesting that microsatellite analysis may be a useful tool in the primary diagnosis of the disease.

Carcinoma, Squamous Cell↗

PubMed1998

Evaluation of loss of heterozygosity and microsatellite instability in human pterygium: clinical correlations.

AIMS: To evaluate the incidence of loss of heterozygosity (LOH) and microsatellite instability (MI) in pterygia and their possible correlation with clinical variables. METHODS: 50 pterygia, blood, and conjunctival specimens were obtained. A personal and family history was recorded for each patient. Amplification of 15 microsatellite markers at regions 17p, 17q, 13q, 9p, and 9q was performed using the polymerase chain reaction. The electrophoretic pattern of DNA from pterygia was compared with the respective pattern from blood and conjunctiva. RESULTS: LOH incidence was the highest at 9p (48%), followed by 17q (42%). Only three cases displayed MI. LOH incidence at individual markers was positively correlated with recurrence (D9S59, p = 0.11 and D9S270, p = 0.16), family history of neoplasia (D13S175, p = 0.09), altitude of present residence (D9S112, p = 0.1), duration of the existence of pterygium (D9S144, p = 0.06), and inversely correlated with age (D9S59, p = 0.09). Concerning chromosome arms, LOH was positively correlated with the altitude of present residence (13q and 17p, p = 0.03) and duration of the existence of pterygium (13q and 17p, p = 0.09). CONCLUSIONS: LOH is a common event whereas MI is a very uncommon one at the examined markers in pterygium, indicating the presence of putative tumour suppressor genes implicated in the aetiopathogenesis of the disease. The fact that LOH at 9q31-33 was more frequent in recurrent pterygia and also correlated with known risk factors such as young age and high altitude of residence, implies a possible predictive value of this finding for postoperative recurrence.

Adult↗

PubMed1998

Genetic instability in renal cell carcinoma.

OBJECTIVE: To investigate the incidence of loss of heterozygosity (LOH) and microsatellite instability (MI) in human renal cell carcinoma (RCC), and to determine a possible activation of H-ras oncogene in these tumours via implication of its polymorphic regions within the first intron and 3' ends. METHODS: In the present study, we investigated the incidence of MI and LOH in 22 RCCs, using a bank of 8 microsatellite markers located on chromosomes 2 (IL1A), 3 (D3S1234), 8 (MYC), 14 (D14S51) and 17 (THRA1, D17S250, D17S579). We also studied the microsatellite DNA of the H-ras oncogene within the first intron (HRM) and the minisatellite DNA of the variable tandem repeat (VTR), which is located 1,000 bp downstream of the H-ras gene and possesses enhancer activity, for genetic instability. Alterations of the 28-bp repetition core were studied employing restriction fragment length polymorphism analysis. RESULTS: MI and LOH were observed in 8 (4 MI and 4 LOH) out of 22 (18%) specimens at 3p21.1-p14.2 and 17q21, indicating the presence of putative tumour suppressor genes (TSGs) at these loci. Alterations of the 28-bp repetition core of H-ras VTR were found in 2 out of 22 cases (9%), while point mutations of the same repetition core were detected in only 1 case (5%). Additionally, 1 case (5%), showed LOH. CONCLUSIONS: Our results indicate that genetic instability is a detectable phenomenon in human RCC and it might be associated with the development of the disease. LOH at 3p21.1-p14.2 and 17q21 suggests that important TSGs may be located on these chromosomal regions involved in the tumorigenesis or progression of RCC. Considering the fact that the DNA sequence of this VTR region contains a target area for transcription and other regulation factors of H-ras gene expression, these findings could be of importance as regards the involvement of this gene in the process of carcinogenesis in RCC.

Adult↗

PubMed1998

Microsatellite instability and loss of heterozygosity at chromosomes 9 and 17 in non-small cell lung cancer.

BACKGROUND: Microsatellite instability (MI) and loss of heterozygosity (LOH) are described in lung cancer specimens. However, their importance in tumorigenesis remains unknown. The aim of this study was to identify the presence of MI and LOH in human tumor and normal bronchial mucosa DNA. METHODS: We performed biopsies with fiberoptic bronchoscopy and took specimens from the tumor and from the opposite site normal bronchial mucosa in 20 patients with non-small-cell lung cancer (NSCLC). Four patients had an adenocarcinoma, while 16 had a squamous cell carcinoma. Also, 6 patients had an early-stage disease (stages I and II), while 14 patients had an advanced-stage disease (stages III and IV). All paired specimens were studied for MI and LOH on chromosome 17p, 17q, 9p, and 9q, with 10 polymorphic markers. RESULTS: Sixteen of 20 tumors displayed genetic alterations (80%). Six tumors (30%) exhibited MI, five tumors (25%) exhibited LOH, while five tumors exhibited MI and LOH concurrently. The marker HBX had the most frequent incidence of LOH (4/20, 20%), indicating that the hbx gene becomes a strong candidate tumor suppressor gene, whereas of MI it was D17S515 (4/20, 20%). No relationship was observed between the presence of LOH or MI and the histologic subtype of NSCLC or the stage of the disease. CONCLUSION: Results suggest that genetic alterations exist in tumor, compared with the normal mucosa DNA. They may have a role in carcinogenesis as they exist in all stages and in both NSCLC histologic subtypes studied.

Adenocarcinoma↗

PubMed1997

Microsatellite instability and loss of heterozygosity in human pterygia.

AIMS/BACKGROUND: Pterygium is a common benign lesion of the corneoconjunctival limbus. Although environmental factors, such as ultraviolet irradiation, have been suggested as the main causative factor in the development of the disease, however, the aetiopathology of pterygium remains obscure. In this study the possibility of detecting genetic alterations in the microsatellite DNA of the pterygium was investigated. METHODS: Fifteen specimens were assessed for for loss of heterozygosity (LOH) and microsatellite instability (MI) by seven microsatellite markers on four chromosomal arms. RESULTS: Nine (60%) pterygia exhibited genetic alterations. Eight specimens (53%) exhibited LOH, while two specimens (13%) MI in at least one marker. 17q11.2-q21 is a commonly deleted region, as the frequency of LOH at this region is significantly high (47%). CONCLUSION: This finding indicates the existence of tumour suppressor genes in this region implicated in the disease without excluding the presence of other tumour suppressor genes in the other chromosomal regions that were examined. MI was apparent in only a few specimens but it is indeed a detectable phenomenon, suggesting that decreased fidelity in DNA replication and repair may be associated with the development of pterygium. Detection of LOH and MI, two events taking place in tumour cells or in premalignant cells, constitutes strong evidence that there must be transformed cells in the pterygial tissue and it should be considered to be a neoplastic benign lesion.

Female↗

PubMed1997

Microsatellite instability and loss of heterozygosity in primary breast tumours.

Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour suppressor genes. We looked for evidence of microsatellite instability (MI) and LOH on chromosome 7q, 10q, 11p and 17q using seven polymorphic microsatellite markers. In 42 paired breast cancer-peripheral blood DNA samples we identified 24 tumours (57%) exhibiting genetic alterations. Twenty-one specimens exhibited LOH (50%), while 11 specimens exhibited MI (26%) in at least one microsatellite marker. The most frequent incidence of LOH was found for the marker THRA1 (8/33, 24%) indicating that thra I gene becomes a strong candidate tumour suppressor gene, whereas of MI it was D10S109 (3/26, 12%). These MI and LOH data were analysed using a range of clinicopathological parameters. Tumours displaying MI with no evidence of LOH and tumours exhibiting MI and LOH belonging to stage II or III were found, however none were at stage I. These data suggest that MI may be an early event in mammary tumorigenesis whereas LOH occurs at a late stage. A significant association between the absence of oestrogen receptors (p < 0.01) and the absence of both oestrogen and progesterone receptors (p < 0.001) at 17q21 were observed, indicating a possible relationship between specific genetic changes at this region and hormonal deregulation in the progression of breast cancer.

Adult↗

PubMed1995

Loss of heterozygosity at 9p and 17q in human laryngeal tumors.

Recent investigations revealed that the 9p arm and 17q arm of human chromosomes harbour tumour suppressor genes (TSGs) with an important role in multistage carcinogenesis. At the 9p arm is located the p16 (MTS1) TSG and probably others with an effect on various human tumours such as acute lymphoblastic leukaemia, bladder cancer, gliomas, malignant mesotheliomas, melanomas and non-small cell lung carcinomas. In addition, the 17q arm harbours BRCA1 TSG which is responsible for approximately 80% of the familial breast/ovarian cancer cases. In order to investigate the implication of these performed a loss of heterozygosity (LOH) analysis with 10 polymorphic microsatellite markers (three at the 17q arm surrounding the BRCA1 region and seven at the 9p arm). Fourteen of the 17 (82%) tumours exhibited deletions at 9p. The highest incidence of LOH (6/13, 46%) was found for the marker D9S157 at 9p22. One sample exhibited deletion of all the informative markers tested indicating deletion of the complete 9p arm. No homozygous deletions were found. LOH at the 17q arm near the BRCA1 locus was found in 6 (35%) among 17 specimens. The results of this study indicate that allelic deletions at 9p are frequent in the development of laryngeal tumours. The highest incidence of LOH was found for the marker D9S157 which is near, but distinct from the location of p16 (MTS1) tumour suppressor gene, indicating the presence of multiple tumour suppressor genes within this chromosomal region. In addition, BRCA1 TSG is implicated in the development of laryngeal tumours.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Von Hippel-Lindau tumour suppressor gene is not involved in sporadic human breast cancer.

OBJECTIVE: Mutations of the von Hippel-Lindau (vhl) gene, as well as allelic loss at the gene region (3p25-26) have been described in sporadic cases of the tumour types participating in VHL disease, but also in cancers not associated with the syndrome. In this study, we attempted mutation analysis of the vhl gene, as well as detection of allelic loss at 3p25-26 in sporadic human breast cancer. METHODS: Eighty-two tumour specimens were screened for loss of heterozygosity (LOH) at the vhl region, and compared to the adjacent, histologically normal tissue. Furthermore, mutations within the three exons of vhl in the same panel of tumours were detected using SSCP and heteroduplex analysis and direct sequencing. RESULTS: To our knowledge this is the first mutational analysis reported for the vhl gene in breast cancer, however we failed to reveal any mutations in the specimens examined. All the cases were informative for at least one of the microsatellite markers tested, 24 (29.2%) exhibited LOH at 3p25-26. Clinical and pathological data were available for all tumours examined, however no significant correlations were encountered. CONCLUSION: These results strongly indicate against a critical involvement of the tumour suppressor vhl in breast carcinogenesis.

Breast↗

PubMedDate not supplied

Loss of heterozygosity on chromosomes 1, 2, 8, 9 and 17 in cerebral atherosclerotic plaques.

OBJECTIVE: Atherosclerosis is a fibroproliferative disease which has been attributed to several factors including genetic and molecular alterations. Initial studies have shown genetic alterations at the microsatellite level in the DNA of atherosclerotic plaques. Extending our initial findings, we performed a microsatellite analysis on cerebral atherosclerotic plaques. METHODS: Twenty-seven cerebral atherosclerotic plaques were assessed for loss of heterozygosity (LOH) and microsatellite instability (MI) using 25 microsatellite markers located on chromosomes 2, 8, 9 and 17. DNA was extracted from the vessels as well as the respective blood from each patient and subjected to polymerase chain reaction. RESULTS: Our analyses revealed that specific loci on chromosomes 2, 8, 9 and 17 exhibited a significant incidence of LOH. Forty-six percent of the specimens showed loss of heterozygosity at 2p13-p21, 48% exhibited LOH at 8p12-q11.2, while allelic imbalance was detected in 47% of the cases. The LOH incidence was 39%, 31% and 27% at 17q21, 9q31-34 and 17p13, respectively. Genetic alterations were detected at a higher rate as compared to the corresponding alterations observed in plaques from other vessels. DISCUSSION: This is the first microsatellite analysis using atherosclerotic plaques obtained from cerebral vessels. Our results indicate an elevated mutational rate on specific chromosomal loci, suggesting a potential implication of these regions in atherogenesis.

Chromosomes, Human, Pair 1↗