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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The small-cell lung carcinoma cell line U2020 contains a submicroscopic, homozygous deletion that removes a chromosomal segment within 3p13-p14, including the locus D3S3. We have sublocalized 49 additional probes to the 3p13-p14.2 region and have identified 7 new DNA markers that arise from within the U2020 deletion. The estimated size of the deletion, based on marker density, is approximately 4-5 megabases (Mb). Including D3S3, 7 of the 8 markers have been linked by pulsed-field gel (PFG) electrophoresis over an area of approximately 2 Mb. Including the one unlinked marker, PFG analysis accounts for about 3 Mb of the region. The U2020 deletion appears confined to the 3p13-p14.2 region and does not include the candidate tumor suppressor gene, protein-tyrosine phosphatase gamma (PTPG).
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PMID:Characterization of the submicroscopic deletion in the small-cell lung carcinoma (SCLC) cell line U2020. 138 64

The tumors of patients with small cell lung carcinoma (SCLC) frequently exhibit the loss of alleles at polymorphic loci on the short arm of chromosome 3. We report the genotype analysis of six SCLC patients obtained using 15 chromosome 3 probes that identified 19 restriction fragment length polymorphisms (RFLPs). Five of the six patients were reduced to homozygosity in the tumor DNA at every informative 3p locus, and thus did not serve to delineate the deletion. However, the RFLP analysis of the tumor DNA of the sixth patient demonstrated both heterozygous and hemizygous loci on 3p and allowed the definition of an interstitial deletion that extends proximal to the D3S2 locus at 3p14.2-p21 to include at least 3p13-p14. The exclusion of the D3F15S2 locus from the deleted region, observed in this patient, is an uncharacteristic feature of SCLC deletions. This deletion includes the location of D3S30 and D3S4, and thus serves to map these loci within the proximal half of chromosome 3.
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PMID:An unusually proximal deletion on the short arm of chromosome 3 in a patient with small cell lung cancer. 167 84

Five polymorphic DNA segments from human chromosome 3, that are frequently deleted in lung carcinoma were mapped by non-isotopic in situ hybridization to metaphase chromosomes. The DNA segment D3S3 mapped to 3p13-p14.2, D3S6 to 3p14.3-p14.5, D3S48 to distal 3p21-p22, ERBA beta to 3p24.3 and ERBA2 to 3p24.3. The map location of ERBA beta and ERBA2 was confirmed by re-mapping each probe in combination with D3S6 as a marker for 3p14.
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PMID:Localization of polymorphic DNA probes frequently deleted in lung carcinoma. 255 Mar 53

A translocation between chromosomes 3 and 8, t(3;8)(p14.2;q24.13), has been reported in a family with hereditary renal cell carcinoma. Using somatic cell hybrids, we have isolated, separately, both derivative chromosomes. We find that the c-myc oncogene (8q24.1) has been translocated to the derivative 3 [der(3)]. We have not detected a rearrangement within an approximately equal to 21-kilobase region around the c-myc gene using restriction enzyme digestion and Southern blot hybridization analysis. The translocated c-myc gene should provide a probe to the chromosome 3p14 region, which appears to be important not only in renal cell carcinoma but also in small cell carcinoma of the lung. These hybrids have also been useful for the regional mapping of the Chinese hamster ovary cell Gly-B defect to 8q22.1----q24.13 and support the regional assignment of acylase I to 3p21.
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PMID:Translocation of c-myc in the hereditary renal cell carcinoma associated with a t(3;8)(p14.2;q24.13) chromosomal translocation. 299 98

The common fragile site at 3p14(FRA3B) is cytogenetically close to the positions of translocation and deletion breakpoints frequently observed in renal cell carcinoma (RCC) and small cell carcinoma of the lung. Possible involvement of this fragile site in the familial RCC t(3;8)(p14.2;q24.1) was investigated. Expression of FRA3B, induced by treatment of lymphocytes with aphidicolin, is altered by the translocation. These results suggest that the fragile site is very close to, if not coincident with, the translocation breakpoint.
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PMID:Translocation t(3;8)(p14.2;q24.1) in renal cell carcinoma affects expression of the common fragile site at 3p14(FRA3B) in lymphocytes. 312 59

Nearly all clear cell renal cell carcinomas (RCCs) exhibit loss of alleles on the short arm of chromosome 3. Loss and mutation at the von Hippel-Lindau (VHL) gene at 3p25 probably occurs in most RCCs and, since the VHL gene was recently cloned, data on VHL involvement in RCCs is accumulating. However, the region 3p14-p12, a region that contains the familial RCC-associated t(3;8)(p14.2;q24) chromosome translocation and the small cell lung carcinoma-associated homozygous deletion at 3p13-12, has also been reported to exhibit allele loss in a large fraction of RCCs. In order to focus future studies on potential suppressor genes in the 3p14-p12 region, we have studied allele loss in 30 RCCs with 9 polymorphic simple sequence repeat markers spanning 3p21.1-p12. Partial losses in the 3p21-p12 region were observed, allowing determination of common regions of loss of heterozygosity overlap in 15 RCCs. Results suggested that most RCCs exhibit loss in a region which brackets the t(3;8) familial chromosome translocation at 3p14.2, and some show additional deletions within the U2020 small cell lung carcinoma deletion at 3p12.
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PMID:Common regions of deletion in chromosome regions 3p12 and 3p14.2 in primary clear cell renal carcinomas. 803 88

We previously characterized and cloned a unique human hepatic dihydrodiol dehydrogenase (DDH) that exhibits high affinity binding for bile acids (Stolz, A., Hammond, L., Lou, H., Takikawa, H., Ronk, M., and Shively, J. E. (1993) J. Biol. Chem. 268, 10448-10457). This hepatic dihydrodiol dehydrogenase demonstrates significant sequence homology with the cytosolic rat bile acid binder 3 alpha-hydroxysteroid dehydrogenase and other members of the monomeric oxidoreductase gene family. We now report the genomic organization and chromosomal localization of the human hepatic DDH in order to further define its physiological role and provide additional insight into the development of this gene family. The 15-kilobase human hepatic DDH gene was contained in an overlapping cosmid and lambda genomic clones and is composed of nine exons. A major transcriptional start site was determined to be 30 base pairs upstream from the ATG initiation methionine by both primer extension and S1 nuclease mapping studies. The human hepatic DDH gene was mapped by chromosomal in situ hybridization and analysis of human-mouse somatic cell hybrids to the tip of the short arm of chromosome 10 at p14. Strict conservation of the intron-exon junctions in the human hepatic DDH and two other members of the monomeric oxidoreductase gene family, aldose reductase and mouse major vas deferens protein suggests evolution from a common ancestral gene. Human hepatic DDH mRNA was identified in both human hepatoma Hep G2 and human lung carcinoma cell line NCI-H322 by RN'ase protection; thus, these cell lines will be useful in examining the regulation of the gene.
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PMID:Genomic organization and chromosomal localization of a novel human hepatic dihydrodiol dehydrogenase with high affinity bile acid binding. 813 67

We have isolated and mapped by fluorescence in situ hybridization 80 new cosmids on the short arm of chromosome 3. These markers were isolated from a radiation-reduced hybrid, DM1, made from a cell line that was monochromosomal for human chromosome 3. Selected cosmids were used in double-label cohybridization experiments in which polymerase chain reaction products, generated by an Alu oligonucleotide primer from genomic DNA, were used for chromosome banding. Fifty-six of the cosmid probes map between 3p14.3 and 3p22 while 24 other probes cluster around bands 3p23-3p25. Three probes that appeared to map close to the chromosome 3 region bearing a t(3,8)p14.2; q24.1 translocation associated with renal cell carcinoma were analyzed by interphase mapping techniques and hybridized to metaphase spreads from the translocation cell line. These 80 probes will be useful in the elucidation of genetic alterations associated with diseases such as small cell lung carcinoma, renal cell carcinoma, and von Hippel-Lindau disease.
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PMID:Isolation and FISH mapping of 80 cosmid clones on the short arm of human chromosome 3. 848 89

A new human cancer cell line was established from a metastatic lesion of a small cell lung carcinoma (SCLC-R1) and maintained in continuous culture with a doubling time of 62 h. The SCLC-R1 line, whose ultrastructural features are presented, showed a diploid DNA content, a translocation involving chromosome 16 [t(16;?)(q24;?)] and noticeable deletions in the FHIT (fragile histidine triad) region in the short arm of chromosome 3 [del(3)(p14)] and in the telomeric region of the short arm of chromosome 12 [del(12)(p13)]. The involvement of 12p in metastatic small cell lung cancer is reported here for the first time. No amplification or rearrangements were evident in the c-myc, L-myc, N-myc, int-2, c-erbB-2, H-ras, K-ras, c-mos, and hst-1 genes by Southern blot analysis. Wild-type p53, RB, K-ras and H-ras genes were evident by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. The neuron specific enolase (NSE) level was much higher in the cell line's cytosol than in the patient's serum and the cell line also had high expression of chromogranin A and cytokeratin 19. SCLC-R1 cells were sensitive to cisplatin, carboplatin and doxorubicin. The clinical history of the patient from whom the cell line was derived is reported. The characteristics of this new cell line indicate it to be a useful experimental model to investigate lung cancer biology and anticancer drug response.
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PMID:Chromosomal alterations, biological features and in vitro chemosensitivity of SCLC-R1, a new cell line from human metastatic small cell lung carcinoma. 971 81

While p14(ARF) suppression of tumorigenesis in a p53-dependent manner is well studied, the mechanism by which p14(ARF) inhibits tumorigenesis independently of p53 remains elusive. A variety of factors have been reported to play a role in this latter process. We report here that p14(ARF) displays different effects on the anchorage-dependent and -independent growth of p53-null/Mdm2 wild type cells. p14(ARF) blocks both the anchorage-dependent and-independent (soft agar) proliferation of 293T and p53(-/-) HCT116, but not p53-null H1299 lung carcinoma cells. While p14(ARF) had no effect on the anchorage-dependent proliferation of p53(-/-) MEFs and Ras12V-transformed p53(-/-) MEFs, it inhibited the growth of Ras12V-transformed p53(-/-) MEFs in soft agar. Furthermore, ectopic expression of p14(ARF) did not lead to degradation of the E2F1 protein and did not result in the reduction of E2F1 activity detected by two E2F1 responsible promoters, Apaf1 and p14(ARF) promoter, in 293T, p53(-/-) HCT116, and H1299 cells. This is consistent with our observations that p14(ARF) did not result in G1 arrest, but induced apoptosis via Bax up-regulation. Taken together, our data demonstrate that the response of p53-null cells to ARF is cell type dependent and involves factors other than Mdm2 and E2F1.
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PMID:p14ARF inhibits the growth of p53 deficient cells in a cell-specific manner. 1676 54


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