Abstract：
:A single cancer cell contains large numbers of genetic alterations that in combination create the malignant phenotype. However, whether amplified and mutated genes form functional and physical interaction networks that could explain the selection for cells with combined alterations is unknown. To investigate this issue, we characterized copy number alterations in 191 breast tumors using dense single nucleotide polymorphism arrays and identified 1,747 genes with copy number gain organized into 30 amplicons. Amplicons were distributed unequally throughout the genome. Each amplicon had distinct enrichment pattern in pathways, networks, and molecular functions, but genes within individual amplicons did not form coherent functional units. Genes in amplicons included all major tumorigenic pathways and were highly enriched in breast cancer-causative genes. In contrast, 1,188 genes with somatic mutations in breast cancer were distributed randomly over the genome, did not represent a functionally cohesive gene set, and were relatively less enriched in breast cancer marker genes. Mutated and gained genes did not show statistically significant overlap but were highly synergistic in populating key tumorigenic pathways including transforming growth factor beta, WNT, fibroblast growth factor, and PIP3 signaling. In general, mutated genes were more frequently upstream of gained genes in transcription regulation signaling than vice versa, suggesting that mutated genes are mainly regulators, whereas gained genes are mostly regulated. ESR1 was the major transcription factor regulating amplified but not mutated genes. Our results support the hypothesis that multiple genetic events, including copy number gains and somatic mutations, are necessary for establishing the malignant cell phenotype.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Nikolsky Y,Sviridov E,Yao J,Dosymbekov D,Ustyansky V,Kaznacheev V,Dezso Z,Mulvey L,Macconaill LE,Winckler W,Serebryiskaya T,Nikolskaya T,Polyak Kdoi
10.1158/0008-5472.CAN-08-3082subject
Has Abstractpub_date
2008-11-15 00:00:00pages
9532-40issue
22eissn
0008-5472issn
1538-7445pii
68/22/9532journal_volume
68pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Previous studies have shown dose-dependent growth inhibition of the human mammary carcinoma cell line MDA-MB-231 xenotransplanted in athymic mice using retinol. In this study, the growth inhibitory effect of retinoic acid (RA) and 13-cis-retinoic acid (13-cis-RA) was examined in vitro and in vivo. With both agents the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:Antineoplastic drug resistance is a major obstacle to improved treatment of most adult cancers in humans. Novobiocin, an antibacterial agent which inhibits the eukaryotic topoisomerase II enzyme, increases the cytotoxicity of several alkylating agents in vitro by the formation of lethal DNA-DNA interstrand cross-links...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-01-15 00:00:00
abstract：:Monoclonal antibodies (Mabs) against human ovarian mucinous and serous carcinoma were obtained by the Mab technique. Their reactivities against human tumors were tested by indirect immunofluorescence. One of the Mabs, named 4C7, derived from the spleen cells of mice immunized with mucinous carcinoma line OVA-1, reacte...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion; however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the re...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3534
更新日期：2015-06-15 00:00:00
abstract：:After 5 or 20 mg cyclophosphamide per kg body weight, given once i.v., the output in thoracic duct lymph of small and large lymphoid cells, cells incorporating [3H]lymidine in vitro, mitotic cells, pyknotic cells, and/or the number of lymphocytes and neutrophils in peripheral blood were measured in six calves. The med...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:An investigation was carried out to determine the potential for activating tumor-inhibitory macrophages with the cytotoxic antitumor agent, bisantrene. Macrophages prepared from peritoneal exudates of mice treated i.p. with bisantrene were extremely active in inhibiting the growth of tumor cells. The minimal effective...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-06-01 00:00:00
abstract：:A multilaminar alteration of endoplasmic reticulum (ER) has been observed in tumor cells of eight patients with Hodgkin's disease and a patient with histiocytic lymphoma. These multilaminar structures are more numerous in dividing cells and thus appear to arise primarily during mitosis. The stacked membranes in the mu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:Chromatin was isolated from 0.025 M citric acid nuclei of regenerating rat liver at 1,5,18,24, and 48 hr posthepatectomy. The total protein to DNA ratios did not change significantly during this time period. However, 2-dimensional polyacrylamide gel electrophoresis of nonhistone proteins of "Chromatin Fraction II" rev...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-05-01 00:00:00
abstract：:The fate of circulating tumor cells is an important determinant of their ability to form distant metastasis. Here, we demonstrate the use of in vivo flow cytometry as a powerful new method for detecting quantitatively circulating cancer cells. We specifically examine the circulation kinetics of two prostate cancer cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1058
更新日期：2004-08-01 00:00:00
abstract：:Oligomerization of the nonreceptor tyrosine kinase c-Abl can activate its transforming potential. Domains mediating oligomerization within the BCR-ABL and TEL-ABL oncoproteins are required for transforming activity, and fusion of inducible dimerization domains to c-Abl can generate chimeric proteins with dimerization-...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-02-15 00:00:00
abstract：:Three groups of 6 to 8-week-old male mice with transplanted C57BL/6 X DBA/2F1 tumor were irradiated by a single dose of 60Co localized on the tumor in association with i.p. injections of lyophilized Bacillus Calmette-Guérin. When the animals were sacrificed, tumor parameters (weight, surface area, and volume) were det...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-05-01 00:00:00
abstract：:O6-Alkylguanine, a DNA adduct formed by nitrosoureas, becomes the site of a point mutation during DNA synthesis by preferentially base mispairing with thymine rather than correctly base pairing with cytosine. To repair this adduct, cells contain a limited amount of O6-alkylguanine-DNA alkyltransferase (alkyltransferas...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:The requirement for cell division in the malignant transformation of A31-714 cells, a subclone derived from BALB/3T3, by 3-methylcholanthrene was investigated using the property of the high susceptibility of this clone to density-dependent inhibition of cell growth. Treatment with 3-methylcholanthrene did not induce t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-07-01 00:00:00
abstract：:Primary central nervous system lymphoma (PCNSL) that arises in immune-deficient patients is an aggressive B-cell neoplasm that is universally associated with the EBV. Patients with EBV(+) PCNSL face a particularly poor prognosis with median survival times of 2-12 months despite aggressive management with radiation the...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-03-01 00:00:00
abstract：:Elucidation of the mechanism by which oxaliplatin induces cell death is essential to enhancing its action. We investigated the effects of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin (17-AAG) in a panel of four colon adenocarcinoma cell lines. Cytotoxicity assays demonstrated at least additivity in three of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-15 00:00:00
abstract：:We investigated primary human lung cancers resected surgically or obtained at autopsy. Included were squamous cell carcinoma (SQC) (five cases), adenocarcinoma (ADC) (six cases), large cell carcinoma (LCC) (four cases), and small cell carcinoma (SCC) (two cases). The objective of the study was to search for the presen...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-04-15 00:00:00
abstract：:Although apoptosis and necrosis are morphologically distinct manifestations of cell death, apoptosis and some necroses share common features in the death signaling pathway involving functional steps of death-driving interleukin 1beta-converting enzyme family proteases and anti-cell death protein Bcl-2. One evident phy...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-05-15 00:00:00
abstract：:MicroRNAs are noncoding RNAs that inhibit the expression of their targets in a sequence-specific manner and play crucial roles during oncogenesis. Here we show that microRNA-7 (miR-7) inhibits p21-activated kinase 1 (Pak1) expression, a widely up-regulated signaling kinase in multiple human cancers, by targeting the 3...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-2103
更新日期：2008-10-15 00:00:00
abstract：:Expression of transforming growth factor beta 1 (TGF beta 1) protein was examined in chemically induced benign skin tumors with genetically defined empirical risks for malignant conversion. Benign tumors induced in mice which have both alleles of the p53 gene deleted have a malignant conversion frequency of approximat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-11-15 00:00:00
abstract：:Claudin proteins form a large family of integral membrane proteins crucial for tight junction formation and function. Our previous studies have revealed that claudin-3 and claudin-4 proteins are highly overexpressed in ovarian cancer. To clarify the roles of claudins in ovarian tumorigenesis, we have generated human o...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1036
更新日期：2005-08-15 00:00:00
abstract：:The three-dimensional structures of two carcinogens, 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[ai1anthracene, have been determined by X-ray crystallographic techniques. Both compounds are carcinogenic and are believed to act by alkylating DNA. However, the first has a nonplanar ring system, wher...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:Angiogenesis, the sprouting of new blood vessels from existing vessels, occurs in many physiological and pathological processes, including embryonic development, wound healing, and tumor growth. It is required for tumor growth because new blood vessel formation is necessary for tumors to expand beyond a minimum volume...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:One set of genes sufficient for transformation of primary human cells uses the combination of Ha-Ras-V12, the telomerase catalytic subunit hTERT, SV40 large tumor antigen (LT), and SV40 small tumor antigen (ST). Whereas SV40 LT inactivates the retinoblastoma protein and p53, the contribution of ST is poorly understood...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1150
更新日期：2004-10-01 00:00:00
abstract：:Ionizing radiation is a major tool for cancer treatment. The response of eukaryotic cells to ionizing radiation includes apoptosis, a process which requires activation of multiple genes. We sought to determine whether radiation-induced gene expression plays a role in radiation-induced apoptosis. We found Apo2 ligand (...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-10-15 00:00:00
abstract：:Soluble membrane fractions derived from polyoma tumor cells trigger lymphocytes, derived from polyoma-immunized animals, but not from nonimmunized controls, to release the lymphokine, macrophage migration-inhibitory factor. The reaction can be blocked by sera from polyoma-bearing animals. Absorption of these sera with...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:Severe weight loss is associated with many malignant diseases of humans and animals. Avian reticuloendotheliosis viruses (RE viruses) induce runting in experimentally infected chickens. Chickens infected with a replication-competent RE virus, reticuloendotheliosis-associated virus, weighed 30-50% less than control bir...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:Diets high in red and processed meats are associated with carcinogenesis of the large intestine, but no prospective study has examined meat and fat intake in relation to cancer of the small intestine. We prospectively investigated meat and fat intakes, estimated from a food frequency questionnaire, in relation to smal...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-2015
更新日期：2008-11-15 00:00:00
abstract：:We report here the use of viral fusogenic membrane glycoproteins (FMGs) as a new class of therapeutic genes for the control of tumor growth. FMGs kill cells by fusing them into large multinucleated syncytia, which die by sequestration of cell nuclei and subsequent nuclear fusion by a mechanism that is nonapoptotic, as...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-03-15 00:00:00
abstract：:Heat shock protein 70 (HSP70) inhibits apoptosis and thereby increases the survival of cells exposed to a wide range of lethal stimuli. HSP70 has also been shown to increase the tumorigenicity of cancer cells in rodent models. The protective function of this chaperone involves interaction and neutralization of the cas...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-12-01 00:00:00
abstract：:Several studies have shown that neuroblastoma and retinoblastoma tumor cells often have elevated N-myc mRNA levels compared to normal adult neuronal or retinal tissues, and it has been suggested that increased expression of this protooncogene may play an important role in tumorigenesis or malignant progression in cell...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
