No abstract available.
Adenocarcinoma* ; Loss of Heterozygosity*

No abstract available.
Colorectal Neoplasms* ; Loss of Heterozygosity*

BACKGROUND/AIMS: The status of tumor suppression gene can be assessed indirectly by analyzing the loss of heterozygosity. Hepatoblastoma is a malignant liver tumor in childhood. To find the molecular carcinogenetic mechanism of hepatoblastoma, loss of heterozygosity (LOH) of p73, APC and p53 was studied. MATERIALS AND METHODS: Hepatoblastoma tissues from thirty-three cases were collected by lobectomy or tumorectomy. On H- stained sections, normal and tumor cells were microdissected separately and LOH analysis was perfomed using 8 markers: six of p73, one of APC and one of p53. RESULTS: Number of cases showing at least one LOH in six p73 markers was four out of twenty- six (15.4%): each LOH frequencies in D1S160, D1S170, D1S199, D1S228, D1S243 and D1S253 were in order of 7.7%, 0%, 9.1%, 0%, 12.5% and 0%. LOH frequency of APC was 41.7% and that of p53 was 13.3%. CONCLUSION: Low LOH frequency of p73 related markers indicates that p73 gene may not be implicated in carcinogenesis of hepatoblastoma.
Carcinogenesis ; Hepatoblastoma* ; Liver ; Loss of Heterozygosity*

No abstract available.
Genetic Loci* ; Loss of Heterozygosity* ; Stomach Neoplasms*

OBJECTIVETo establish stable techniques of comparative genomic hybridization (CGH) and apply them to elucidate the genetic characteristics of hepatoblastoma (HB), and to explore the characteristics and clinical significance of loss of heterozygosity (LOH) at 1p36 in HB.

METHODSCGH was employed to detect the genomic imbalance (DNA loss or amplification) in 20 cases of HB, and PCR-simple repeated sequence polymorphism was employed in 30 cases of HB to detect the loss of heterozygosity for 6 satellites at chromosome 1p36.

RESULTSThere were different chromosome variations for each HB. chromosome amplification was frequently seen in 1q, 2q,2p, 8q, 8p, 12q and 22q. Chromosome loss was often seen in 1p, 4q, 4p, 16q, 17p and 18q. The frequency of LOH at 6 loci on chromosome 1 was 63.3% totally (19/30), with the highest D1S199 (66.7%) and D1S450 next to it (46.7%).

CONCLUSIONThere were chromosome zones with DNA amplification or loss in hepatoblastoma. There are extensive LOH at 1p36 in hepatoblastoma. The corresponding amplification of oncogene and loss of antioncogene may take part in the development of hepatoblastoma.

Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 1 ; genetics ; Female ; Hepatoblastoma ; genetics ; Humans ; Liver Neoplasms ; genetics ; Loss of Heterozygosity ; Male ; Nucleic Acid Hybridization ; methods

OBJECTIVETo evaluate and map the putative tumor suppressor loci on chromosome 5 involved in tumor progress or metastasis.

METHODSChromosome 5 of 83 patients with sporadic colorectal cancer was systemically screened. Fifteen microsatellite marker primers labeled with 3 different fluorescents were used to amplify the corresponding loci of the genome DNA. The PCR products were electrophoresed on a 377 PRISM sequencer and the fluorescent signals were analyzed with Genotyper and Genescan software.

RESULTSThe highest loss of heterozygosity (LOH) ratio was found at D5S416 (48.15%) on 5p and at D5S471 (38.71%) on 5q. The region (5q13.3 - 31), where D5S471 and 3 neighboring loci (D5S428, D5S2027 and D5S2115) reside, presented high frequent LOH.

CONCLUSIONThe deletion of APC, MCC, CTNNA1 and IL cluster in the 5q 13.3 - 31.1 area play important role in the tumorogenesis of colorectal cancer, and the expected existence of another novel tumor suppressor gene on 5p is possible.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; Colorectal Neoplasms ; genetics ; Female ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; genetics ; Middle Aged

The objectives of this study were to characterize the alterations of 3p and 9p in sporadic renal cell carcinomas (RCC) and to assess the relationship between the clinical stages or tumor size and the alteration of these chromosomes. Thirty eight archival, paraffin embedded tissue sections from 38 patients with RCC were analyzed for loss of heterozygosity (LOH) at 3p and 9p with 11 microsatellite markers. LOH was detected in 81.6% (31/38) and 37.8% (14/37) at 3p and 9p, respectively. The frequencies of LOH at VHL and FHIT locus were 75.6% and 72.2%, respectively. Twelve cases out of 38 showed LOH at both 9p21 and 3p. The loss of 3p in the samples tested was not related to clinical stages and tumor size, but that of 9p21 was significantly associated with advanced stage and larger tumor size. These results support that 3p deletion, including VHL and FHIT gene, play a critical role in the tumorigenesis of sporadic RCC, especially at early stage, and that 9p21 may contribute to the progression of sporadic RCC.
Carcinogenesis ; Carcinoma, Renal Cell* ; Humans ; Loss of Heterozygosity* ; Microsatellite Repeats ; Paraffin

OBJECTIVE: Allelic losses or loss of heterozygosity (LOH) at many chromosomal loci have been found in the cells of meningiomas. The objective of this study was to evaluate LOH at several loci of different chromosomes (1p32, 17p13, 7q21, 7q31, and 22q13) in different grades of meningiomas. METHODS: Forty surgical specimens were obtained and classified as benign, atypical, and anaplastic meningiomas. After DNA extraction, ten polymorphic microsatellite markers were used to detect LOH. Medical and surgical records, as well as pathologic findings, were reviewed retrospectively. RESULTS: LOH at 1p32 was detected in 24%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. Whereas LOH at 7q21 was found in only one atypical meningioma. LOH at 7q31 was found in one benign meningioma and one atypical meningioma. LOH at 17p13 was detected in 4%, 40%, and 80% in benign, atypical, and anaplastic meningiomas, respectively. LOH at 22q13 was seen in 48%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. LOH results at 1p32 and 17p13 showed statistically significant differences between benign and non-benign meningiomas. CONCLUSION: LOH at 1p32 and 17p13 showed a strong correlation with tumor progression. On the other hand, LOH at 7q21 and 7q31 may not contribute to the development of the meningiomas.
DNA ; Hand ; Loss of Heterozygosity ; Meningioma ; Microsatellite Repeats ; Retrospective Studies

PURPOSE: Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric cancer were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis. MATENRIALS AND METHODS: To correlate DNA and RNA lesions of the FHIT gene with the effect on FHIT protein expression, in 40 gastric cancers, we investigated the FHIT gene for loss of heterozygisity (LOH), aberrant transcripts, and protein expression. RESULTS: Allelic loss at D3S1300 was detected in 7 of 38 (19%) informative cases. Aberrant transcripts were observed in 20 of 40 (50%) cases. Significant reduction of FHIT protein expression was observed in 22 of 40 (55%) cases. Aberrant FHIT transcription was shown to be associated with loss of FHIT protein expression. However, aberrent FHIT transcripts themselves were not associated with any clinicopathological parameters, such as age, sex, tumor site, or clinical stage. Moreover, there was no association between the presence of LOH at D3S1300 and the expression of aberrant FHIT transcripts. CONCLUSION: The high frequency of aberrant FHIT transcripts, the significant rate of LOH at D3S1300, and the altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.
Carcinogenesis ; DNA ; Gene Expression* ; Histidine* ; Loss of Heterozygosity ; RNA ; Stomach Neoplasms*

PURPOSE: MicroRNAs (miRNAs) are a major class of small endogenous RNA molecules that posttranscriptionally regulate the expression of most genes in the human genome. miRNAs are often located in chromosomal fragile sites, which are suscept-ible to amplification or deletion. Chromosomal deletions are frequent events in breast cancer cells. Deletion and loss of heterozygosity at 17p13.3 have been reported in 49% of breast cancers. The aim of the current study was to evaluate potential expression alterations of miR-22, miR-132, and miR-212, which are located on the 17p13.3 locus and are required for mammary gland development. METHODS: A matched case-control study was conducted, which included 36 pairs of tumor and matched nontumor surgical specimens from patients diagnosed with breast invasive ductal carcinoma. Formalin-fixed paraffin-embedded samples from archival collections at the pathology department of Shariati Hospital were prepared for RNA extraction using the xylene-ethanol method before total RNA was isolated with TRIzol Reagent. Specific primers were designed for cDNA synthesis and miRNA amplification. The expression of miRNAs was then evaluated by real-time polymerase chain reaction (RT-PCR). RESULTS: According to our RT-PCR data, the miR-212/miR-132 family was downregulated in breast cancer (0.328-fold, p<0.001), and this reduced expression was the most prominent in high-grade tumors. In contrast, miR-22 exhibited a significant upregulation in breast tumor samples (2.183-fold, p=0.040). CONCLUSION: Consistent with the frequent deletion of the 17p13.3 locus in breast tumor cells, our gene expression data demonstrated a significant downregulation of miR-212 and miR-132 in breast cancer tissues. In contrast, we observed a significant upregulation of miR-22 in breast tumor samples. The latter conflicting result may have been due to the upregulation of miR-22 in stromal/cancer-associated fibroblasts, rather than in the tumor cells.
Biomarkers ; Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Case-Control Studies ; Chromosome Deletion ; DNA, Complementary ; Down-Regulation ; Fibroblasts ; Gene Expression ; Genome, Human ; Humans ; Loss of Heterozygosity ; Mammary Glands, Human ; Methods ; MicroRNAs* ; Pathology ; Real-Time Polymerase Chain Reaction ; RNA ; Up-Regulation