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Biomedical subjects

M Emi

Publications and source records attributed to M Emi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Allelic loss on chromosome 1p is associated with progression and lymph node metastasis of primary breast carcinoma.

BACKGROUND: Frequent allelic losses on the short arm of chromosome 1 have been observed in a wide variety of human tumors. Cytogenetic and molecular genetic studies in breast carcinomas have shown frequent alterations on chromosome 1, involving loss of 1p or gain of 1q. METHODS: To define the locations of tumor suppressor genes, 143 primary breast carcinomas were examined for allelic loss using 15 highly polymorphic microsatellite markers on 1p. Correlations also were sought between allelic loss on 1p and several clinicopathologic parameters. RESULTS: Allelic loss was observed in 73 of the tumors (51%). Detailed deletion mapping identified target regions at 1p36, 1p34-p35, and 1p22-p31. Allelic losses at 1.36 or 1p34-p35 were observed more frequently in tumors of the solid tubular and scirrhous types than in less aggressive histologic types. Conversely, allelic loss at 1p22-p31 was correlated with lymph node metastasis and a tumor size > 2 cm. CONCLUSIONS: Inactivation of tumor suppressor genes that lie in either 1p36 or 1p34-p35 might affect carcinogenic mechanisms in a histologic type specific manner, especially the solid tubular and scirrhous types. Alterations of one or more tumor suppressor genes at 1p22-p31 may play a role at late stages of breast carcinogenesis, especially with regard to local progression and lymph node metastasis.

Adenocarcinoma↗
PubMed1998

Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the human estrogen receptor beta locus.

A gene for a second type of human estrogen receptor, the estrogen receptor beta (ESR beta), was recently identified. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human estrogen receptor beta gene. High heterozygosity (0.93) makes this polymorphism a useful marker in the genetic study of disorders affecting female endocrine systems; calcium metabolism; and breast, uterine, and ovarian cancers.

Alleles↗
PubMed1998

Isolation and radiation hybrid mapping of dinucleotide repeat polymorphism at the human matrix Gla protein (MGP) locus.

Matrix Gla protein (MGP) is an 84-residue, vitamin K-dependent protein expressed by chondrocytes and vascular smooth muscle cells, and is a potent regulator of calcium deposition in cartilage and arterial wall. We isolated a polymorphic dinucleotide CA repeat marker from a genomic clone containing the human MGP gene. This polymorphism will be useful in genetic studies of arteriosclerosis and osteoporosis.

Alleles↗
PubMed1998

A polymorphic CA repeat sequence at the human calcitonin locus.

A polymorphic dinucleotide (CA) repeat sequence was isolated from a genomic clone containing the human calcitonin gene at 11p15.2-p15.1. This polymorphism will be a useful marker in the genetic study of disorders affecting calcium metabolism including hyperparathyroidism, hypoparathyroidism, and osteoporosis.

Alleles↗
PubMed1998

Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene.

In the course of investigations of familial coronary artery disease in Hokkaido, the northern island of Japan, we identified five families in which multiple members showed elevated plasma levels of low-density lipoprotein (LDL) cholesterol. To determine the genetic etiology of their lipoprotein abnormalities, we screened DNA samples from these families for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor (LDLR) gene. Novel point mutations were identified in each family: (1) a C-to-A transversion at nucleotide 285, causing a nonsense mutation at codon 74, in eight members of family A; (2) a G-to-A transition at nucleotide 1136, causing substitution of Tyr for Cys at codon 358, in six members of family B; (3) a C-to-T transition at nucleotide 1822, causing substitution of Ser for Pro at codon 587, in five members of family C; (4) a one-base insertion of G to a five-G stretch at nucleotides 1774-1778 (codons 571-572), causing a frameshift, in six members of family D; and (5) a one-base deletion of T at nucleotide 1963-1964 (codon 634), causing a frameshift, in three members of family E. Through the molecular genetic approach a total of 28 individuals in these families were diagnosed unequivocally as heterozygous for the respective LDLR mutations. This method also helped us to diagnose familial hypercholesterolemia, or to exclude from carrier status, 11 children with borderline high cholesterol levels.

Adolescent↗
PubMed1998

A highly polymorphic CA repeat marker at the human tumor necrosis factor alpha (TNFA alpha) locus.

Tumor necrosis factor alpha (TNF alpha) in activated monocytes exerts cytotoxic activity and has a variety of other biological effects. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the gene located at 6p21.3. High heterozygosity (0.80) makes this polymorphism a useful marker in the genetic study of disorders affecting immunological response and cell differentiation.

Alleles↗
PubMed1998

Isolation and radiation hybrid mapping of a dinucleotide repeat polymorphism at the human calcium-sensing receptor (CASR) locus.

Calcium-sensing receptor (CASR) in parathyroid gland regulates calcium homeostasis by sensing decreases in extracellular calcium levels and effecting an increase in secretion of parathyroid hormone. A polymorphic dinucleotide (CA) sequence was isolated from a genomic clone containing the human CASR gene and was mapped to 3q13.3-q21. This polymorphism will be useful in the genetic study of disorders affecting calcium metabolism, such as hypercalcemia, hypocalcemia, osteoporosis, hyperparathyroidism, and hypoparathyroidism.

Alleles↗
PubMed1998

Identification of a new commonly deleted region within a 2-cM interval of chromosome 11p11 in breast cancers.

Allelic loss has been observed on the short arm of chromosome 11 in a variety of human cancers. We have examined 184 breast cancers for allelic loss anywhere in chromosome 11p, using 15 well-spaced microsatellite markers. Allelic loss was observed in 86 cases (47%) and a new commonly deleted region 2-cM in length was identified at 11p11 between loci D11S986 and D11S1313, in addition to a 12-cM region of a common deletion at 11p15.5. A significant association was found between allelic loss on 11p15.5 and LOH on 11p11 and the loss of progesterone receptors.

Autoradiography↗
PubMed1998

A novel missense mutation and frameshift mutations in the type II receptor of transforming growth factor-beta gene in sporadic colon cancer with microsatellite instability.

Microsatellite instability of DNA samples of 79 sporadic colon cancer patients were analyzed. These samples were also screened to search mutations in the repeat sequences in the gene for the type II receptor of transforming growth factor-beta (TGF-beta RII) using polymerase chain reaction (PCR), electrophoresis with urea gel, and PCR-single strand conformation polymorphism (PCR-SSCP) method. The incidence of microsatellite instability, defined as severe replication error phenotype (RER) with microsatellite alterations in more than three loci, was 6%. Deletion and insertion of an A residue in the (A)10 region, which cause frameshift mutation, were found in four samples and their incidence in the samples with microsatellite instability was 80%. A novel nucleotide substitution of T for G at 1918, which causes missense mutation of arginine to leucine at codon 528, was found in a sample with microsatellite instability. The mutation at 1918 was in highly conservative amino acid residue.

Colonic Neoplasms↗
PubMed1998

Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers.

To detect BRCA1 mutations in Japanese breast cancer patients, we screened 1,000 unselected primary cancers for mutations in exon 11, which accounts for 61% of the entire BRCA1 coding sequence. Using a method based on multiplex single-strand conformational polymorphism (SSCP) analysis of multiple restriction fragments generated by restriction-enzyme digestion of amplified DNA, we identified eight mutations. All eight were germline mutations; four of them were non-sense mutations or small deletions resulting in premature stop codons, and the other four were missense mutations. The Japanese carriers of these mutant BRCA1 alleles had developed breast cancers at ages ranging from 45 to 62, five of them bilaterally.

Aged↗
PubMed1998

Somatic mutations of the PTEN/MMAC1 gene in fifteen Japanese endometrial cancers: evidence for inactivation of both alleles.

Loss of heterozygosity (LOH) of chromosome 10q is observed in approximately 40% of endometrial cancers. Mutations in PTEN/MMAC1, a gene recently isolated from the 10q23 region, are responsible for two dominantly inherited neoplastic syndromes, Cowden disease and Bannayan-Zonana syndrome. Somatic mutations of this gene have also been detected in sporadic cancers of the brain, prostate and breast. To investigate the potential role of this putative tumor suppressor gene in endometrial carcinogenesis as well, we examined 46 primary endometrial cancers for LOH at the 10q23 region, and for mutations in the entire coding region and exon-intron boundaries of the PTEN/MMAC1 gene. LOH was identified in half of the 38 informative cases, and subtle somatic mutations were detected in 15 tumors (33%). Our results suggest that of the genes studied so far in endometrial carcinomas, PTEN/MMAC1 is the most commonly mutated one, and that inactivation of both copies by allelic loss and/or mutation, a pattern that defines genes as "tumor suppressors," contributes to tumorigenesis in endometrial cancers.

Alleles↗
PubMed1998

Allelic loss on chromosome 9q is associated with lymph node metastasis of primary breast cancer.

Frequent allelic losses on chromosome 9 are seen in a wide variety of human tumors; moreover, two genes (P16 and PTC) whose mutant alleles confer predispositions to some inherited cancer syndromes have been identified on this chromosome. Using 15 highly polymorphic microsatellite markers distributed on both arms of chromosome 9, we tested 96 primary breast carcinomas for allelic loss in order to define the locations of genes that might be involved in this type of tumor. Allelic loss was observed in 37 of the tumors (39%) and detailed deletion mapping identified target regions at 9p21, 9q22.3 and 9q33. Losses at 9q22.3 and 9q33 were correlated with the presence of lymph node metastasis, and allelic loss at 9q22.3 was observed more frequently in scirrhous tumors than in less aggressive histologic types. Therefore, inactivation of tumor suppressor genes in 9q22.3 and 9q33 regions might play a role in progression of breast cancers, especially in metastasis to lymph nodes and in development of scirrhous tumors.

Adenocarcinoma, Scirrhous↗
PubMed1998

Frequent allelic loss at 7p14-15 associated with aggressive histologic types of breast cancer.

We examined 142 primary human breast cancers to determine their patterns of loss of heterozygosity (LOH) at 19 microsatellite markers over the entire length of chromosome 7. Allelic loss at one or more loci on the short arm of chromosome 7 was observed in 37 of the tumors (26%). We found a new target region of allelic loss on 7p between D7S1802 and D7S817 at 7p14-15. LOH on 7p was found more frequently in tumors of the invasive solid tubular and scirrhous type (31 of 87); 36%) than in other less aggressive types (2 of 27; 7%) (P = 0.0047). The results suggest that inactivation of putative tumor suppressor gene(s) located at 7p14-15 may play a role in the development and/or progression of primary breast cancers, particularly those of the invasive solid tubular and scirrhous type. Allelic loss was also found in 56 of 142 tumors on the long arm, and a commonly deleted region was defined between D7S522 and D7S1801 at 7q31.

Breast Neoplasms↗
PubMed1998

Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) in East Asia is a distinctive chronic obstructive pulmonary disease of unknown etiology. We hypothesize that the disease susceptibility is due to genetic predisposition unique to Asians. Association between human leukocyte antigen (HLA)-Bw54 and the disease was previously reported. In the present study, using newly developed polymerase chain reaction (PCR)- based methods, we directly analyzed HLA class I and II alleles in 76 Japanese patients. HLA-A, -B, and -C antigens were screened by the conventional typing method, and then B22-group alleles including HLA-B54 were genotyped by single-strand conformation polymorphism analysis. Alleles of HLA-DRB1 gene were fully determined by the microtiter plate hybridization method. Thirty-seven percent of the patients possessed HLA-B*5401 allele conserved predominantly in East Asians, as compared with 15% of 110 healthy volunteers (chi2 = 12.4, p = 0.0004). In addition, 4% of the patients possessed B*5504 also unique to Asians but a rare allele which was not found in normal control subjects in this study. Typing of HLA-DRB1 class II gene did not demonstrate strong positive association with the disease. A33, B44, and DRB1*1302 showed negative association with the disease. We conclude that distinctive molecular structure of HLA-B alleles or a closely linked gene in the HLA region contributes to genetic predisposition in diffuse panbronchiolitis. This may partly explain why this disorder is found primarily in Asians.

Alleles↗
PubMed1998

Molecular genetic diagnosis of a family with hypercholesterolemia by a mismatched PCR-RFLP method for genotyping single base substitution of the LDL receptor gene.

Plasma lipid and lipoprotein levels reflect in part the influence of relevant genetic loci. Defects at some of these loci account for specific types of dyslipoproteinemia occurring with regularity among family members. In the course of familial investigations of coronary artery disease, we identified an family in which several members were affected with elevated low density lipoprotein (LDL) cholesterol levels. To study the genetic defects responsible for plasma lipoprotein abnormality in this pedigree, we developed a simple method for genotyping a single base substitution that does not affect a restriction recognition enzyme site in exon 10 of the LDL receptor gene. Using our mismatched PCR method, this G- > A substitution at nucleotide 1413 could be genotyped in the form of a biallelic restriction fragment length polymorphism (RFLP) after digestion with restriction enzyme Hpa II. Linkage analysis using this molecular method demonstrated that the defect at the LDL receptor locus is responsible for elevated LDL cholesterol phenotype observed in this family by segregation of defective alleles at the LDL receptor locus with the disease (peak decimal logarithm of odds score > 3.0).

Adolescent↗