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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
PubMed1999

Two target regions of allelic loss on chromosome 9 in urinary-bladder cancer.

Allelic losses on chromosome 9 are common in a wide variety of human tumors; moreover, two predisposing loci for some inherited cancer syndromes, i.e., familial malignant melanoma and Gorlin syndrome, have been identified on this chromosome. To define the location of putative tumor suppressor genes involved in cancer of the urinary bladder, 85 bladder cancers were examined for allelic loss at 18 microsatellite loci on chromosome 9. Correlations were also sought between loss of heterozygosity on chromosome 9 and several clinicopathological parameters. Allelic loss was observed in 54 of the tumors (64%) and deletion mapping identified two target regions; one at an interval on 9p21 flanked by D9S736 and D9S165, and the other at an interval on 9q31-34 flanked by D9S58 and D9S61. No subtle mutation was detected in the PTCH gene which lies in the latter interval. Allelic loss on chromosome 9 was observed frequently in low grade and non-invasive tumors as well as in tumors of more advanced phenotype. Inactivation of tumor suppressor genes lying in either of two regions of common deletion identified on chromosome 9 might affect carcinogenic mechanisms at an early stage of tumor development in the urinary bladder.

Chromosome Mapping↗
PubMed1999

Familial hypercholesterolemia in Utah kindred with novel 2412-6 Ins G mutations in exon 17 of the LDL receptor gene.

Familial hypercholesterolemia (FH) is a monogenic disorder associated with primary hypercholesterolemia. FH is characterized by autosomal co-dominant inheritance with strikingly elevated LDL-cholesterol, the presence of xanthoma and premature atherosclerosis. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To determine the genetic etiology of the lipoprotein abnormalities, we screened DNA samples from the family for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein receptor (LDLR) gene. Novel point mutations were identified in the proband: a one-base insertion of G to a five-G stretch at nucleotides 2412-6 (codons 783-785), causing a frameshift in exon 17 of the LDL receptor gene. The direct sequencing method was used to examine six members of the family recruited for the diagnosis. This method helped to unequivocally diagnose the five individuals as heterozygous for this particular LDL receptor mutation. This method also helped us to diagnose with FH, or to exclude from carrier status, three children between ages 6 and 11.

Child↗
PubMed1999

Familial hypercholesterolemia in Utah kindred with novel R103W mutations in exon 4 of the LDL receptor gene.

Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein cholesterol levels early in childhood and very early coronary disease in both men and women. Previously published blood cholesterol criteria greatly under-diagnosed new cases of FH among members of known families with FH and over-diagnosed FH among participants of general population screening. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To carry out molecular genetic diagnosis of the disease, we screened DNA samples for mutations in all 18 exons and the exon- intron boundaries of the low-density lipoprotein (LDL) receptor gene. Novel point mutations were identified in the proband: a C-to-T transversion at nucleotide position 369, causing substitution of Tryptophan for Arginine at codon 103 in exon 4 of the LDL receptor gene. The SSCP method was used to examine seven members of the family recruited for the diagnosis. This method helped to unequivocally diagnose only the proband as heterozygous for this particular LDL receptor mutation while excluding the remaining six individuals from carrier status with FH.

Adolescent↗
PubMed1999

Identification of a 1-cM region of common deletion on 4q35 associated with progression of hepatocellular carcinoma.

To identify the location of one or more of the putative tumor suppressor genes (TSG) on chromosome arm 4q that may be involved in hepatocellular carcinoma (HCC), we examined 96 primary HCCs for their patterns of allelic loss at 39 microsatellite marker loci distributed along this chromosome arm. Allelic loss at one or more loci was observed in 71 (74%) HCCs. Detailed deletion mapping identified two distinct commonly deleted regions; one was located within a 1-cM interval flanked by D4S1534 and D4S2929 at 4q21-22, the other in the 1-cM interval flanked by D4S2921 and D4S2930 at 4q35. Of the tumors for which clinical data were available, allelic loss at 4q35 was more frequent in poorly or moderately differentiated tumors than in well-differentiated tumors (3/15, 20%, vs. 14/21, 67%, P = 0.008); in tumors larger than 2 cm in size (2/11, 18%, vs. 34/62, 55%, P = 0.046); and in tumors that arose from liver cirrhosis as opposed to HCCs arising from chronic hepatitis (25/42, 60%, vs. 9/27, 33%, P = 0.048). The association of allelic losses on 4q35 with larger tumor size and aggressive histological type implies that loss or inactivation of TSG located within the 1-cM interval of 4q35 identified here contribute to progression of HCCs.

Carcinoma, Hepatocellular↗
PubMed1999

Identification of a I-cM region of common deletion on 13q14 associated with human prostate cancer.

Frequent allelic losses on chromosome arm 13q are observed in carcinomas of the head and neck, breast, ovary, and pituitary gland. We analyzed 59 primary prostate tumors (stage B, 18 patients; C, 12 patients; D1, 4 patients; and endocrine therapy-resistant cancer death, 25 patients), as well as 18 metastatic tissues from 14 of the 25 cancer death patients for loss of heterozygosity (LOH) using 35 microsatellite markers on chromosome arm 13q. Of the 59 primary tumors, 31 (53%) showed LOH involving at least one locus. Detailed deletion mapping identified a distinct commonly deleted region in the I-cM interval flanked by D13S153 and D13S273 on 13q14 and this region overlapped a part of the RB1 gene. Paired DNAs were available from both primary and metastatic tumors in the 14 cases of cancer death; among those pairs, we detected LOH on 13q in seven (50%) primary tumors, and in all metastatic foci (P = 0.0029). Moreover, the regions lost in metastatic tissues were more extensive than those seen in the corresponding primary tumors. These results suggest that inactivation of a putative tumor suppressor gene(s) including the RB1 gene on 13q14 plays an important role in human prostate cancer.

Adrenal Gland Neoplasms↗
PubMed1999

Allelic loss at 1p34, 13q12, 17p13.3, and 17q21.1 correlates with poor postoperative prognosis in breast cancer.

Allelic losses of tumor suppressor genes (TSGs), or the chromosomal regions harboring them, in tumor DNA may become useful postoperative prognostic indicators. To examine whether specific allelic losses might correlate with postoperative survival in a 5-year prospective follow-up, we tested tumors from a cohort of 264 breast cancer patients for allelic losses of 18 microsatellite markers representing either a known TSG or a region where genetic alterations are frequent in breast tumors. Patients whose tumors had lost an allele at 1p34, 13q12, 17p13.3, or 17q21.1 had significantly higher risks of postoperative mortality than those whose tumors retained both alleles at those loci (at 1p34, a 5-year mortality rate of 29% among patients with losses vs. 7% with retentions, P = 0. 0008; at 13q12, 31% vs. 10%, P = 0.0062; at 17p13.3, 24% vs. 13%, P = 0.026; and at 17q21.1, 31% vs. 13%, P = 0.0047). Furthermore, combined losses at 13q12 and 17p13.3 increased the predicted postoperative mortality risks by a factor of 9.6 (5-year mortality rate of 42% vs. 5% with retentions, P = 0.0001), and combined losses at 1p34 and 17p13.3 raised the predicted postoperative mortality risks by a factor of 8.6 (27% vs. 3%, P = 0.0064). We conclude that allelic losses at these loci can serve as negative prognostic indicators to guide postoperative management of patients. Genes Chromosomes Cancer 26:134-141, 1999.

Adult↗
PubMed1998

Frequent Allelic Loss at 6q26-27 in Breast Carcinomas of the Solid-tubular Histologic Type.

To characterize the effect that inactivation of a putative tumor suppressor gene on 6q appears to have on breast carcinogenesis, we examined loss of heterozygosity in 528 primary breast carcinomas with a polymorphic marker located at 6q26-27, a frequent target region of allelic loss in ovarian and breast cancers. Ofthe 56 informative tumors of the solid-tubular type, 29(52&precnt;)showed allelic lossat 6q26-27;however, only 10 of 42 papillotubular carcinomas(23%)and 34 of 86 scirrhous carcinomas(39%)showed allelic loss(p = 0.0215). These results are consistent with reported alterations at 6q26-27 in serous and mucinous types of ovariancancers, in that they suggest that inactivation of one or more genes in that region may affect carcinogenic mechanisms in a histologic type-specific manner in neoplasms of the female reproductive organs.

Journal Article↗
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↗