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V V Murty

Publications and source records attributed to V V Murty.

At least 55 records · Page 3Linked to original sources
PubMed1994

Loss of heterozygosity and decreased expression of NME genes correlate with teratomatous differentiation in human male germ cell tumors.

Embryonal carcinoma in the human male is a pluripotential germ cell tumor (GCT), which is suggested to further differentiate to teratoma which displays somatic differentiation representing all three germinal layers. In a panel of 37 GCTs we determined frequency of loss of heterozygosity (LOH) and the level of expression of nucleoside diphosphate kinase (NDPK) genes NME 1 and NME 2. The frequency of LOH in teratomas (86%) was found to be highly significant (P < 0.01) compared to embryonal carcinomas (17%). We also found that the NME encoded proteins are expressed at a 4-5 fold lower level in teratomas compared to embryonal carcinomas. These findings lead us to hypothesize that a critical level of NDPK may be necessary for suppression of aberrant somatic differentiation.

Gene Expression↗
PubMed1994

Transforming growth factor receptor gene TGFBR2 maps to human chromosome band 3p22.

In this study, we map the chromosomal position of the gene that encodes the type II receptor of TGF-beta (HGM symbol TGFBR2), a multifunctional regulator of cell proliferation and differentiation. Using a full-length cDNA and a genomic probe in Southern blot analysis of a human x rodent somatic cell hybrid panel and by direct fluorescence in situ hybridization to normal metaphase chromosomes, we show that the TGFBR2 gene maps to 3p22.

Animals↗
PubMed1994

ERBB2 (HER2/neu) oncogene is frequently amplified in squamous cell carcinoma of the uterine cervix.

We evaluated a panel of 22 protooncogenes for amplification in 50 primary, untreated squamous cell carcinomas of the uterine cervix. The tumors studied belonged to clinical stages II and III; histologically, the majority of them were moderately to well differentiated. Amplification represented by 5 or more copies was observed for the genes MYCL1, SEA, CCND1, BCL1, and GLI in one case each (2%); HRAS in 2 cases (4%); and ERBB2 in 7 cases (14%). Amplification of ERBB2 ranged from 5 to 68 copies. In addition, 2 tumors with ERBB2 amplification showed additional restriction fragments suggesting possible mutation or rearrangement of the gene. The high incidence of ERBB2 amplification in cervical cancer suggests that this gene may play an important role in tumorigenesis.

Carcinoma, Squamous Cell↗
PubMed1994

Subregional mapping of 8 single copy loci to chromosome 6 by fluorescence in situ hybridization.

We have subregionally mapped 8 independently derived probes which have been assigned to chromosome 6 (D6S61, D6S134, D6S149, D6S155, MACS, VIL2, IGF2R and PLG) by FISH. All the probes were mapped to the long arm of chromosome 6 except D6S61, which was assigned to the short arm at 6p25. The remaining probes were clustered at the 6q25-->q27 region except MACS which was mapped to 6q22.2.

Chromosome Mapping↗
PubMed1994

Allelic loss and somatic differentiation in human male germ cell tumors.

The complex but poorly understood human male germ cell tumors offer unusual opportunities for the genetic analysis of malignant transformation and embryonal differentiation in a pluripotential stem cell lineage. Histologically, these tumors are divided into two major subgroups, seminomas which are characterized by inability to express embryonal differentiation, and non-seminomas which are characterized by ability to express embryonal as well as extra-embryonal patterns of differentiation. To understand the role of genetic factors in the development of these tumors and the regulation of differentiation expressed by them, we carried out a detailed allelotype analysis by the loss of heterozygosity assay. This analysis revealed frequent deletions in known tumor suppressor genes (RB1, DCC, NME), a number of previously described sites of candidate tumor suppressor genes (3p, 9p, 9q, 10q, 11p, 11q and 17p), as well as several novel sites (2p, 3q, 5p, 12q, 18p and 20p). Our results also showed that well differentiated teratomas exhibit a significantly higher level of allelic loss compared to the less differentiated embryonal carcinomas. In addition, certain loci and genes exhibited frequent non-random deletion in teratomas (D3S32, D3S42, D5S12, D10S25, D11S12, RB1, TP53, NME1, NME2, D17S4, D18S6 and D20S6) and embryonal carcinomas (IFNB, D9S27). Among these loci, the NME genes were notable for a high degree of genetic loss (> 70%) in teratomas. These results suggested that nonrandom loss or inactivation of certain genes may be associated with tumor development and loss or inactivation of other genes may be associated with somatic differentiation.

Alleles↗
PubMed1994

Frequent allelic deletions and loss of expression characterize the DCC gene in male germ cell tumors.

The DCC tumor suppressor gene has been shown to be frequently deleted or its expression reduced or absent in colorectal, gastro-intestinal, pancreatic, prostatic, and breast carcinomas, and glioblastomas. By allelotype analysis using the DCC-flanking polymorphic marker D18S5 we have previously shown that allelic deletions at 18q21 occur in 40% of male germ cell tumors (Murty et al., 1994). In order to further understand the role of DCC gene in germ cell tumorigenesis, we evaluated deletions by loss of heterozygosity (LOH) and mRNA expression by RT-PCR in tumor tissues and cell lines. Analysis of 61 paired normal-tumor DNAs using the probes D18S5, JOSH 4.4 (a polymorphism within the DCC locus) and a (CA)n polymorphism in an intron of DCC revealed that 45% of GCTs had allelic deletions. In addition, two homozygous deletions were found in the DCC gene among 91 (61 used in the LOH analysis and an additional 30) tumor DNAs when screened with the cDNA probes (pDCC 1.65, pDCC 1.9 and pDCC 1.0). By RT-PCR analysis of four normal testes, nine GCT cell lines and 14 tumor tissues, DCC gene expression was detected in all four normal testes, while four (45%) GCT cell lines and one (7%) tumor specimen showed lack of expression. In addition, DCC expression was highly reduced in three (21%) tumor tissues. The high frequency of LOH at 18q21 was characteristic of seminomas as well as all subsets of non-seminomas in primary as well as metastatic states. Frequent allelic loss in all histologic subsets, homozygous deletions, and loss of expression of DCC suggest that suppression of this gene's function is an early event in GCT development.

Alleles↗
PubMed1993

Subregional localization of 20 single-copy loci to chromosome 6 by fluorescence in situ hybridization.

Although 338 genetic loci and 1 or more candidate tumor suppressor genes have been assigned to chromosome 6, the physical and genetic map of this chromosome is at a very preliminary stage. In this study, we have performed subregional localization of 20 single-copy DNA sequences previously assigned to chromosome 6 using the fluorescence in situ hybridization technique. One locus, D6S6, was localized at 6p12. Two loci, D6S160 and D6S32, were localized in proximal 6q, at 6q12 and 6q23.3, respectively. The remaining loci were clustered in two regions, 4 at 6q23.5-q25 (D6S33, D6S43, D6S85, MYB) and 13 at 6q26-q27 (D6S2, D6S21, D6S22, D6S25, D6S37, D6S39, D6S44, D6S48, D6S132, D6S133, D6S148, D6S170, D6S201). These data will aid in the eventual development of the physical map of chromosome 6.

Chromosome Mapping↗
PubMed1993

Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2.

Human metastasis-suppressor genes nm23-1 (NME1) and nm23-2 (NME2) are implicated in control of the metastatic potential of malignant cells. Using somatic cell hybrid analysis and fluorescence in situ hybridization we co-localized both genes to 17q21.3. The 17q21 region carries the locus responsible for early-onset familial breast-ovarian cancer and several other genes that are involved in tumorigenesis and differentiation and undergo frequent rearrangements during neoplastic development. Thus, our mapping places the NME genes in a region that may be subjected to multiple selection pressures. NME1 and NME2 genes were expressed as soluble proteins in a T7 bacterial expression system. Both proteins are independently active nucleotide diphosphate kinases and readily form intra- and intermolecular disulfide bonds. The biochemical properties of these proteins may explain the diversity of mature eucaryotic nucleoside diphosphate kinases.

Animals↗
PubMed1993

Chromosomal localization of genes encoding the transcription factors, c-rel, NF-kappa Bp50, NF-kappa Bp65, and lyt-10 by fluorescence in situ hybridization.

We have used fluorescence in situ hybridization (FISH) to perform precise chromosomal mapping of the genes encoding the transcription factors c-rel, NF-kappa Bp50, NF-kappa Bp65, and lyt-10. The previously published assignments of c-rel and NF-kappa Bp50 have been refined to specific bands. The map position of lyt-10, inferred from its isolation from a t(10;14)(q24;q32) translocation, has been confirmed. NF-kappa Bp65 has now been mapped to 11q13, a site of frequent involvement in aberration in multiple tumor types.

Chromosome Mapping↗
PubMed1992

Allelic deletions in the long arm of chromosome 12 identify sites of candidate tumor suppressor genes in male germ cell tumors.

Human male germ cell tumors (GCTs) result from malignant transformation of premeiotic or early meiotic germ cells and exhibit embryonal-like differentiation of the three germinal layers. The genetic basis of origin and expression of differentiated phenotypes by GCTs are poorly understood. Our recent cytogenetic analysis of a large series of GCTs has shown that two chromosome 12 abnormalities, an isochromosome for the short arm [i(12p)] and deletions in the long arm [del(12q)], characterize these tumors, which led us to suggest that the deletions represent loss of one or more candidate tumor suppressor genes whose products regulate the normal proliferation of the spermatogonial stem cells. We undertook a molecular mapping of the deletions by comparing germ-line and tumor genotypes of eight polymorphic loci in paired normal/tumor DNA samples from 45 GCT patients. Analysis of loss of constitutional heterozygosity at these loci revealed two regions of frequent loss (> 40%), one at 12q13 and the other at 12q22, identifying the sites of the postulated tumor suppressor genes. One tumor (no. 143A) exhibited a homozygous deletion of a region of 12q22, which included the MGF gene. The KIT and MGF genes have been shown to play key roles in embryonal and postnatal development of germ cells; therefore, we evaluated their expression by Northern blot analysis in a panel of three GCT cell lines and 24 fresh GCT biopsies. Deregulated expression of MGF and KIT, which was discordant between seminomatous and nonseminomatous lesions, was observed.

Alleles↗
PubMed1992

Assignment of the human TYRP (brown) locus to chromosome region 9p23 by nonradioactive in situ hybridization.

The TYRP (brown) locus determines pigmentation and coat color in the mouse. The human homolog of the TYRP locus has been recently identified and shown to encode a 75-kDa transmembrane melanosomal glycoprotein called gp75. The gp75 glycoprotein is homologous to tyrosinase, an enzyme involved in the synthesis of melanin, forming a family of tyrosinase-related proteins. A genomic clone of human gp75 was used to map the human TYRP locus to chromosome 9, region 9p23, by nonradioactive fluorescent in situ hybridization. Specificity of hybridization was tested with a genomic fragment of human tyrosinase that mapped to a distinct site on 11q21. The 9p region has been reported to be nonrandomly altered in human melanoma, suggesting a role for the region near the TYRP locus in melanocyte transformation.

Chromosomes, Human, Pair 9↗
PubMed1992

Subregional mapping of 13 single-copy genes on the long arm of chromosome 12 by fluorescence in situ hybridization.

Subregional localization of 13 single-copy DNA sequences previously assigned to the long arm of chromosome 12 has been performed using the fluorescence in situ hybridization (FISH) technique. The following order is suggested for the 13 mapped genes: cen-->COL2A1-->(VDR-D12S15)-->(D12S17-D12S4++ +-D12S14-D12S6)-->D12S8-->(IAPP-MGF- D12S7-D12S12)-->IGF1-->qter. Eight of the mapped genes clustered at two regions, one at 12q13 (D12S17-D12S4-D12S14-D12S6) and the other at 12q22 (IAPP-MGF-D12S7-D12S12). Our results show that single-copy DNA sequences as small as 500 bp can be successfully mapped by FISH.

Chromosome Mapping↗
PubMed1992

Detection of cell-cycle stage by fluorescence in situ hybridization: its application in human interphase cytogenetics.

Distinct cell-cycle-dependent changes in the conformation of centromeric chromatin in a specific human chromosome containing alpha-satellite DNA have been demonstrated by fluorescence in situ hybridization (FISH). This method, based upon specific FISH signal morphology, allows simultaneous analysis of chromosomal aneuploidy and detection of specific cell-cycle stage(s) of human tumor and/or normal cell populations in a single preparation of interphase cells. This interphase cytogenetic procedure might prove useful for both basic and clinical research involving human cells.

Cell Cycle↗
PubMed1992

Analysis of BCL2 and MYC expression in non-Hodgkin's lymphomas by in situ hybridization: correlation with chromosome translocations.

We have used an in situ hybridization method for analysis of expression of BCL2 and MYC on cytospun preparations of normal and malignant lymphoid cell lines and tissue sections of normal and malignant lymph nodes. The probes comprised 50-mer antisense oligonucleotides starting at the ATG codons of exon 3 of BCL2 and exon 2 of MYC. We studied the expression of these two genes in frozen tissue sections of biopsy specimens derived from normal and hyperplastic lymph nodes, B-cell lymphomas carrying the t(14;18)(q32;q21) and t(8;14)(q24;q32) translocations, and T-cell lymphomas with clonal chromosome abnormalities. While all proliferating cells expressed both genes, BCL2 expression was increased two- to threefold in follicular lymphomas with t(14;18) and MYC expression was increased two- to four-fold in high-grade lymphomas with t(8;14). These results are consistent with previous data on deregulated expression of these genes obtained from study of lymphoma cell lines carrying the relevant translocations.

Base Sequence↗
PubMed1991

Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.

A unique mRNA produced in leukemic cells from a t(15;17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor alpha (RAR alpha) and a myeloid gene product called PML. PML contains a cysteine-rich region present in a new family of apparent DNA-binding proteins that includes a regulator of the interleukin-2 receptor gene (Rpt-1) and the recombination-activating gene product (RAG-1). Accordingly, PML may represent a novel transcription factor or recombinase. The aberrant PML-RAR fusion product, while typically retinoic acid responsive, displays both cell type- and promoter-specific differences from the wild-type RAR alpha. Because patients with APL can be induced into remission with high dose RA therapy, we propose that the nonliganded PML-RAR protein is a new class of dominant negative oncogene product. Treatment with RA would not only relieve this inhibition, but the activated PML-RAR protein may actually promote myelocyte differentiation.

Amino Acid Sequence↗