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J Inazawa

Publications and source records attributed to J Inazawa.

At least 127 records · Page 7Linked to original sources
PubMed1996

Analysis of numerical aberrations of specific chromosomes by fluorescent in situ hybridization as a diagnostic tool in breast cancer.

BACKGROUND: Biopsy by fine-needle, aspiration has become a routine technique for the diagnosis of a dominant breast mass. In this study, fluorescent in situ, hybridization (FISH) analysis of interphase nuclei allowed the authors to detect genetic aberrations that are difficult to identify by conventional cytology. METHODS: To investigate ways of minimizing misdiagnosis of the cytology of breast tumors, and detecting genetic aberrations preoperatively, the authors performed FISH with specimens obtained by fine-needle aspiration biopsies of 106 primary breast tumors (78 primary breast cancers, 2 phyllodes tumors, and 26 benign breast tumors). Numerical chromosome aberrations were investigated using 3-color FISH performed with (peri)centromere-specific probes for chromosomes 1, 11, and 17. RESULTS: Sufficient materials for FISH analysis were obtained with aspiration biopsy from 98 of the 106 breast tumors (93.4%). None of the benign tumors nor phyllodes tumors showed evidence of aneusomy for any of the 3 chromosomes. However, 71 of the 74 breast cancers (95.9%) for which sufficient material was available demonstrated aneusomy of at least 1 of the 3 chromosomes tested. The FISH analysis also suggested a possible correlation between aneusomy of chromosome 17 and metastasis to regional lymph nodes (chi-square test = 7.78; P < 0.05). CONCLUSIONS: FISH analysis of fine-needle aspiration biopsies can be a practical and useful method for the preoperative diagnosis of breast carcinoma.

Biopsy, Needle↗
PubMed1996

Detailed deletion mapping in squamous cell carcinomas of the esophagus narrows a region containing a putative tumor suppressor gene to about 200 kilobases on distal chromosome 9q.

We previously reported definition of a region containing a putative tumor suppressor gene for esophageal squamous cell carcinoma within an approximately 4-cM genomic segment at 9q31-q32. We have investigated this region further using six new microsatellite markers isolated from yeast artificial chromosome clones covering the deleted region and have narrowly defined the commonly deleted region to a segment between two loci, KM9.1 and D9S177. On the basis of the contig map of cosmid and yeast artificial chromosome clones, we estimate the physical size of the region of interest to be about 200 kb. Because the distal 9q region also has been implicated as the site of a tumor suppressor gene(s) related to squamous cell carcinomas of other tissues, our map provides useful information for attempts to identify a common gene for carcinomas of this cell type.

Base Sequence↗
PubMed1996

Isolation and chromosomal localization of the human cone cGMP phosphodiesterase gamma cDNA (PDE6H).

By comparing lists of 3'-directed partial cDNA sequences (gene signatures) randomly collected from various tissues, genes unique to each tissue can be identified. A full-size cDNA clone, corresponding to one such tissue-specific gene signature that recurred only in a retina library, was isolated and analyzed. This clone encoded 83 amino acids highly homologous to the bovine blue cone cGMP phosphodiesterase gamma subunit. The retina-specific expression of this gene was confirmed by multiple tissue Northern blotting, and its cone specificity was confirmed by in situ hybridization to a human retina specimen. From these results, we concluded that this clone (HGMW-approved symbol PDE6H) encodes for the gamma subunit of human cone-specific cGMP phosphodiesterase, and it was assigned to chromosome 12p13 by fluorescence in situ hybridization.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Molecular cloning and mapping of a human cDNA for cytosolic malate dehydrogenase (MDH1).

We have isolated a human cDNA encoding a protein of 334 amino acids that shows 96% identity in amino acid sequence to murine cytosolic malate dehydrogenase. Heart and skeletal muscle expressed this gene most highly among the adult human tissues examined by Northern blot analysis. By fluorescence in situ hybridization, we determined its chromosomal location to be 2p15.

Adult↗
PubMed1996

PTPN13, a fas-associated protein tyrosine phosphatase, is located on the long arm of chromosome 4 at band q21.3.

PTPN13 is a protein tyrosine phosphatase that associates with the C-terminal negative regulatory domain in the Fas (APO-1/CD95) receptor. The PTPN13 protein contains six GLGF repeats that have been found in the rat postsynaptic density protein (PSD-95) and the Drosophila tumor suppressor protein, lethal-(1)-disc-large-1 (dlg-1). The localization of the PTPN13 gene to human chromosome 4q21.3 was determined by both FISH and PCR analysis of somatic cell hybrids. This 4q21.3 chromosomal region contains a gene for autosomal dominant polycystic kidney disease as well as the region frequently deleted in liver and ovarian cancers, suggesting that PTPN13 is a candidate for one of the putative tumor suppressor genes on the long arm of chromosome 4.

Base Sequence↗
PubMed1996

p53 gene mutation is not directly related to tumoricidal effects of preoperative radiochemohyperthermia therapy for rectal cancers.

BACKGROUND: Several studies have recently demonstrated that apoptosis of cancer cells is triggered by diverse adjuvant cancer therapies and the induction of apoptosis correlates with the sensitivity of the primary tumor to such therapies. METHODS: We investigated the factors modulating adjuvant cancer therapies by examining p53 gene mutations and chromosome 17p allelic losses in 15 rectal cancers treated by a preoperative combined therapy consisting of radiation, intraluminal hyperthermia and 5-fluorouracil suppositories. RESULTS: The point mutations were detected in 7 of 15 (46.7%) tumors by single-stranded conformational polymorphism and direct sequencing. Allelic losses at chromosome 17p were also detected in 7 of 15 (46.7%) tumors by dinucleotide-repeat polymorphisms. There was no correlation between p53 gene abnormalities and the preoperative tumoricidal effect of the therapy. CONCLUSIONS: We conclude that p53 gene abnormalities do not directly increase resistance to the combined adjuvant therapy.

Alleles↗
PubMed1996

Assignment of the human ST2 gene to chromosome 2 at q11.2.

The human St2 locus has been assigned to chromosome 2, using a human ST2 cDNA clone, by a human/rodent somatic cel hybrid mapping panel. The St2 locus has also been mapped to chromosome 2q11.2, using a human ST2 genomic DNA clone, by in situ hybridization. The locus is very tightly linked to the Il-1r1 locus. Together with the structural similarity of ST2 to IL-1RI, these data suggest functional relationships between these two genes.

Animals↗
PubMed1996

Precise localization of the human gene encoding cell adhesion kinase beta (CAK beta/PYK2) to chromosome 8 at p21.1 by fluorescence in situ hybridization.

Cell adhesion kinase beta (CAK beta) is the second protein-tyrosine kinase of the focal adhesion kinase subfamily with large N- and C-domains in addition to the central kinase domain. The cDNA of the human CAK beta has been cloned and used as a probe for the assignment of this gene by fluorescence in situ hybridization. CAK beta is sublocalized on chromosome 8p21.1, a locus frequently involved in allelic losses in colorectal cancers and prostate carcinomas.

Animals↗
PubMed1996

Philadelphia chromosome-negative cells with trisomy 8 after busulfan and interferon treatment of Ph1-positive chronic myelogenous leukemia.

A 48-year-old Japanese man with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) was treated with busulfan followed by interferon-alpha (IFN-alpha). Ten months after IFN-alpha treatment, Ph1(-) cells with trisomy 8 were detected by the conventional banding technique and fluorescence in situ hybridization (FISH) analysis. Add(Y)(q12) was also found in Ph1(-) cells with trisomy 8. Although Ph1(+) cells disappeared after the treatment with IFN-alpha, Ph1(-) cells with trisomy 8 did not. We summarize four previous case reports of Ph1(+) CML developing Ph1(-) cells with trisomy 8. All four patients had received busulfan and IFN-alpha. These drugs may be related to the ontogenesis of Ph1(-) cells with trisomy 8, but the significance of Ph1(-) cells with trisomy 8 is not known, and further observation is needed.

Antineoplastic Agents↗
PubMed1996

Germline mutations of the RET proto-oncogene in pedigree with MEN type 2A: DNA analysis and its implications for pediatric surgery.

To assess the feasibility of screening for multiple endocrine neoplasia type 2A (MEN 2A), the authors used DNA sequence analysis to evaluate the RET proto-oncogene in a kindred with MEN 2A. The kindred consisted of 95 members (1 to 79 years of age) and their spouses, and spanned five generations. Genomic DNA was extracted from peripheral blood lymphocytes or lymphoblastoid cell lines established from the family members, and the RET gene was amplified by polymerase chain reaction (PCR) using RET-specific primers (10q 11.2) and was sequenced. Periodic endocrine screening also was performed, by measuring the plasma calcitonin concentration after provocation with pentagastrin (0.5 microgram/kg intravenously) to assess its reliability for detecting the associated neoplasms. Nineteen patients were confirmed to have MEN 2A by medical records or the screening program. The DNA sequence of the PCR products from clinically established MEN 2A patients showed a mutation at codon 634 (TGC-->CGC) that resulted in an amino acid change from cysteine to arginine. Endocrine screening tests showed that six other family members had a mutated RET protooncogene. DNA sequencing can detect high-risk cases at a preclinical stage of the disease. The establishment of mutated MEN 2A gene carriers allows pediatric surgeons to consider total thyroidectomy at a very early stage of neoplasm development (C-cell hyperplasia) or even prophylactically.

Adolescent↗
PubMed1996

Deletion mapping on chromosome 1p in well-differentiated gastric cancer.

To define the region on the short arm of chromosome 1 that is thought to include one or more tumour-suppressor genes for gastric cancers, we carried out loss of heterozygosity (LOH) studies in 26 gastric adenocarcinomas, using three restriction fragment length polymorphism (RFLP) markers and nine microsatellite markers. All tumours were informative with at least one locus; three revealed replication errors (RERs) at multiple microsatellite loci, and interstitial or telomeric allelic deletions were observed in 12 cases. Deletion mapping of these tumours defined a commonly deleted region between two loci, D1S201 and D1S197, that are 13 cM apart. As two loci within the commonly deleted region, D1S57 (pYNZ2) and D1S62 (pTHI54), were mapped respectively to 1p35 and 1p34.3 by fluorescence in situ hybridisation, we conclude that a locus likely to contain a tumour-suppressor gene for gastric cancer is located within a 13 cM region encompassing two chromosomal bands.

Chromosome Deletion↗
PubMed1996

Molecular cloning of the breakpoint of t(11;22) (q23;q11) chromosome translocation in an adult acute myelomonocytic leukaemia.

Southern blot analysis with a cDNA probe of MLL indicated that the breakpoint is in a BamHI 8.3 kb fragment which carries the exon 5-11 of MLL gene in DNA from an adult acute myelomonocytic leukaemia with a t(11;22) (q23;q11) translocation. The structural analysis of the rearranged MLL locus demonstrated that the breakpoint is localized between exon 8 and 9 of MLL locus. The normal counterpart fused to the MLL locus was proved to be derived from chromosome 22q11(AF-22) by somatic cell hybrids analysis and FISH. By FISH, AF-22 was localized to the region more centromeric to the BCR gene.

Adult↗
PubMed1996

Genomic imprinting of human p57KIP2 and its reduced expression in Wilms' tumors.

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP2 is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS), a cancer syndrome, making it a tumor suppressor candidate. Several types of childhood tumors including Wilms' tumor, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the familial BWS has indicated maternal carriers and suggested a role in genomic imprinting. Previously, we demonstrated that p57KIP2 is imprinted in the mouse. Here we describe the genomic imprinting of human p57KIP2 and the reduction of its expression in Wilms' tumors. High resolution mapping locates p57KIP2 in the region responsible for both tumor suppressivity and BWS.

Alleles↗
PubMed1996

Multiple primary cancers with microsatellite instability: report of a case.

We report here a patient who developed a variety of tumors both synchronously and metachronously over a 2-year period. The involved organs were the uterus, ureter, and small and large intestines. The patient underwent open surgery 3 times and polypectomies 6 times. Postoperative histopathologic analysis showed 2 adenomas and 8 carcinomas. Genetic analysis revealed microsatellite instabilities at the tested loci in all 10 tumors, indicating that replication errors played an essential role in the tumorigenesis. Early identification of microsatellite instability could be useful for predicting development of additional primary cancers.

DNA, Neoplasm↗
PubMed1996

The human homologue of the murine Llglh gene (LLGL) maps within the Smith-Magenis syndrome region in 17p11.2.

We have isolated and characterized the human homologue of the murine Llglh gene, which was originally isolated as a homologue of a Drosophila tumor suppressor gene 1(2)gl (lethal(2) giant larvae). In the mouse, Llglh is thought to play an important role during brain development as a regulatory target of Hoxc8. The human homologue of Llglh (LLGL) encodes a protein consisting of 1,033 amino acids. This gene was mapped by fluorescence in situ hybridization (FISH) to human chromosome 17p11.2, a region that is typically deleted in patients with Smith-Magenis syndrome (SMS). In our FISH analysis of metaphase chromosomes of four SMS patients, a probe representing LLGL failed in each case to hybridize to one of the two chromosome 17 homologues, indicating that this gene may play a role in the pathogenesis of SMS.

Amino Acid Sequence↗
PubMed1996

Isolation and mapping of a human gene (RPD3L1) that is homologous to RPD3, a transcription factor in Saccharomyces cerevisiae.

We have isolated a novel human gene RPD3L1, that is highly homologous to a transcription factor in Saccharomyces cerevisiae, RPD3 (reduced potassium dependency 3), from a human fetal lung cDNA library. The cDNA clone, hRPD3, consists of 2,100 nucleotides that contain an open reading frame of 1446 nucleotides encoding 482 amino acids. It shares 62% identity in nucleotide sequence and 52% identity in amino acid sequence to RPD3. This gene is expressed at various levels in all tissues examined. Furthermore, we were able to map it to chromosome band 1p34.1 by FISH.

3T3 Cells↗
PubMed1996

Isolation and mapping of a human gene (RABL) encoding a small GTP-binding protein homologous to the Ras-related RAB gene.

Many subgroups of the RAB gene, a member of the RAS superfamily have been identified. Here we report the isolation and analysis of a cDNA encoding a putative small GTP-binding protein, designated RABL, from a human fetal lung cDNA library. RABL encodes 216 amino acids that are 86% identical to members of the RAB5 subfamily and it shows 94% homology in nucleotide sequence with RAB5C of dog. This gene was expressed ubiquitously in all human tissues examined. By fluorescence in situ hybridization we mapped RABL to chromosome band 17q21.2.

Amino Acid Sequence↗