Allelic Imbalance ; Genetic Techniques ; Humans

PURPOSE: Allelic deletion of p53 tumor suppressor gene have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. But the loss of heterozygosity (LOH) data on chromosome 17p are rare and controversial with respect to cervical carcinomas. So, we tried to elucidate the frequency of p53 locus LOH in primary cervical carcinoma and compared the LOH data with clinicopathological parameters. MATERIALS AND METHODS: In order to detect LOH within one of the well-known tumor suppressor gene, p53, three intragenic polymorphisms (exon 1, exon 4, and intron 6) and one microsatellite distal to the p53 gene (D17S5) were examined. Paired DNA samples from 55 primary uterine cervical carcinomas and normal bloods were studied for the chromosomal allelic loss of p53 gene locus by polymerase chain reaction (PCR), the presence of human papilloma virus (HPV), and the presence of p53 gene point mutation by PCR-single conformation polymorphism (SSCP) analysis. And the relationships between allelic losses of this gene and conventional clinicopathological parameters were evaluated. RESULTS: We could increase the heterozygosity of the p53 gene up to 1 (100%). The observed allelic loss rate of the p53 locus in informative cases was 5.5% (3/55) and the observed allelic loss rate of the D17S5 locus in informative cases was 8.7% (4/46) . Only one of the four patients with LOH at the D17S5 locus showed a concomittant allelic loss of the p53 gene. The overall LOH incidence of the chromosomal region comprising 17p13.1 (p53) to 17p13.3 (D13S5) was 10.9% (6/55). All the samples contained at least one of the oncogenic HPV type 16 and/or 18 sequences. No shifted bands were observed in the PCR-SSCP analysis of the p53 gene. The LOH of the p53 gene was not related to other parameters including clinical stage, histological type, and degree of differentiation. CONCLUSION: Concerning with the results above, we conclude that the allelic imbalance of the p53 gene itself is not implicated as a major contributing factor in the malignant transformation or the tumor progression in HPV-positive cervical cancers. Another putative tumor suppressor gene which has more important function than p53 gene in cervical carcinogenesis might exist between these two loci [p53 (17p13.1) and D17S5 (17p13.3)].
Allelic Imbalance ; Carcinogenesis ; DNA ; Exons ; Genes, p53* ; Genes, Tumor Suppressor ; Humans ; Incidence ; Introns ; Loss of Heterozygosity* ; Microsatellite Repeats ; Papilloma ; Point Mutation ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms

BACKGROUND: Although the genetic determinants of most sporadic breast cancers remain unknown, the understanding of the molecular and genetic events that contribute to breast carcinogenesis has been significantly advanced. We investigated the clinicopathologic significance of allelic imbalance or mutation of both p53 and PTEN tumor suppressor genes in sporadic breast carcinomas. METHODS: Genomic DNA from 62 breast carcinoma cases was extracted from paraffin blocks, and PCR was performed to determine loss of heterozygosity (LOH) for DNA markers around the p53 and PTEN genes and to amplify exons 5, 6, 7, and 8 of p53 and all 9 coding axons of PTEN. RESULTS: Somatic p53 mutations were detected in 6 (9.7%) of the 62 cases. LOH for DNA markers surrounding p53 was observed in 18 (29.0%) of the 62 cases. LOH for DNA markers surrounding PTEN was detected in 29 (46.8%) of the 62 cases. Only one case (1.6%) showed somatic PTEN mutations. Tumors with LOH on 17p or p53 mutation were large in size and negative for ER, had a high Ki-67 index, and exhibited p53 immunoreactivity (p<0.05). Tumors with LOH on 10q23 were associated with c-erbB-2 positivity (p=0.018). CONCLUSIONS: Our results indicate that LOH at 17p and/or p53 mutation is significantly associated with the aggressive pathologic parameters of breast cancer.
Allelic Imbalance ; Axons ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Clinical Coding ; DNA ; Exons ; Genes, Tumor Suppressor* ; Genetic Markers ; Loss of Heterozygosity* ; Paraffin ; Polymerase Chain Reaction ; PTEN Phosphohydrolase

OBJECTIVETo study the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).

METHODSTen high-polymorphic microsatellite markers on chromosome 8 were selected to detect the loss of heterozygosity (LOH), microsatellite instability (MSI) and allelic imbalance (AI) in 56 HCCs using automatic capillary array electrophoresis DNA analysis system.

RESULTSLOH was found in 37 of 56 HCCs (66.1%) on at least 10 locus. The three most frequently altered loci were D8S261 (53.5%, 23/43), D8S1721 (52.5%, 21/40) and D8S1771 (52.5%, 21/40). LOH on D8S277 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg (P < 0.01). Similarly, LOH on D8S261, D8S298 and D8S1733 occurred more frequently in patients with negative HBsAg than those with positive HBsAg (P < 0.01). LOH on D8S298 and D8S1771 were more frequent in tumors larger than 3 cm in size (P < 0.05 and P < 0.01 respectively). LOH frequencies of D8S1721 were significantly higher in cases with absent or partially encapsulated tumor than in those with intact tumor capsule (P < 0.05). LOH on D8S298 and D8S1771 were more frequently detected in tumors with intrahepatic metastasis than those without (P < 0.01). MSI was found in 12.5% (7/56) cases. AI was found in 19.6% (11/56) of all cases examined.

CONCLUSIONSMicrosatellite alterations on chromosome 8 were frequent in HCC. LOH, possibly representing alterations of the tumor suppressor pathway, may play an important role in hepatocarcinogenesis. MSI, reflecting a dysfunction of the mismatch repair pathway, may also contribute to this process, but in a less significant way. LOH at some particular loci is associated with certain clinicopathological parameters of human HCC.

Adult ; Aged ; Allelic Imbalance ; Carcinoma, Hepatocellular ; genetics ; pathology ; Chromosomes, Human, Pair 8 ; Female ; Humans ; Liver ; pathology ; Liver Neoplasms ; genetics ; pathology ; Loss of Heterozygosity ; Male ; Microsatellite Repeats ; Middle Aged

OBJECTIVETo investigate global genetic alterations in medulloblastoma, and to localize critical chromosomal loci with allelic imbalances associated with the development of medulloblastoma.

METHODSA high-resolution genome-wide allelotype analysis, including 384 microsatellite markers, was performed in 12 medulloblastomas.

RESULTSAn average of 238 (62.3%) allelic imbalances were detected on all 39 autosomal arms. Non-random allelic gains or losses were detected on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). In addition, chromosomal arms with frequencies of allelic imbalances higher than the mean percentage were identified on 3p (33.3%), 3q (33.3%), 4q (41.7%), 7p (33.3%), 8q (41.7%), 10q (41.7%), 13q (33.3%), 14q (33.3%) and 20q (33.3%). No relationship was found between the frequency of allelic imbalances and the clinical outcome of the patients.

CONCLUSIONSA global view of the genetic alterations in medulloblastoma was provided. The allelic imbalances involving chromosomes 7q, 8p, 16q, 17p and 17q may play an important role in the pathogenesis of medulloblastoma.

Adolescent ; Adult ; Alleles ; Allelic Imbalance ; Cerebellar Neoplasms ; genetics ; Child ; Child, Preschool ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 7 ; Chromosomes, Human, Pair 8 ; Female ; Genotype ; Humans ; Male ; Medulloblastoma ; genetics ; Microsatellite Repeats ; genetics

Turner syndrome is one of the most common chromosomal disorders. It is caused by numerical or structural abnormalities of the X chromosome and results in short stature and gonadal dysgenesis. The short stature arises from haploinsufficiency of the SHOX gene, whereas overdosage contributes to tall stature. This report describes the first Korean case of Turner syndrome with tall stature caused by SHOX overdosage. The patient presented with primary amenorrhea and hypergonadotropic hypogonadism at the age of 17 years. Estrogen replacement therapy was initiated at that time. She displayed tall stature from childhood, with normal growth velocity, and reached a final height of 190 cm (standard deviation score, 4.3) at the age of 30 years. Her karyotype was 46,X, psu idic(X)(q21.2), representing partial monosomy of Xq and partial trisomy of Xp. Analysis by multiplex ligation-dependent probe amplification detected a duplication at Xp22.3-Xp22.2, encompassing the PPP2R3 gene near the 5'-end of the SHOX gene through the FANCD gene at Xp22.2.
Amenorrhea ; Chromosome Deletion ; Chromosome Disorders ; Estrogen Replacement Therapy ; Female ; Gonadal Dysgenesis ; Haploinsufficiency ; Humans ; Hypogonadism ; Karyotype ; Multiplex Polymerase Chain Reaction ; Trisomy ; Turner Syndrome* ; X Chromosome

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

Humans ; Amino Acid Metabolism, Inborn Errors/genetics* ; Haploinsufficiency

No abstract available.
Adenocarcinoma* ; Loss of Heterozygosity*

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