Abstract:
:Small cell lung cancer (SCLC) is a disease characterized by aggressive clinical behavior and lack of effective therapy. Owing to its tendency for early dissemination, only a third of patients have limited-stage disease at the time of diagnosis. SCLC is thought to derive from pulmonary neuroendocrine cells. Although several molecular abnormalities in SCLC have been described, there are relatively few studies on epigenetic alterations in this type of tumor. Here, we have used methylation profiling with the methylated-CpG island recovery assay in combination with microarrays and conducted the first genome-scale analysis of methylation changes that occur in primary SCLC and SCLC cell lines. Among the hundreds of tumor-specifically methylated genes discovered, we identified 73 gene targets that are methylated in >77% of primary SCLC tumors, most of which have never been linked to aberrant methylation in tumors. These methylated targets have potential for biomarker development for early detection and therapeutic management of SCLC. SCLC cell lines had a greater number of hypermethylated genes than primary tumors. Gene ontology analysis indicated a significant enrichment of methylated genes functioning as transcription factors and in processes of neuronal differentiation. Motif analysis of tumor-specific methylated regions identified enrichment of binding sites for several neural cell fate-specifying transcription factors including NEUROD1, HAND1, ZNF423 and REST. We hypothesize that two potential mechanisms, loss of cell fate-determining transcription factors by methylation of their promoters and functional inactivation of their corresponding genomic-binding sites by DNA methylation, can promote a differentiation defect of neuroendocrine cells thus enhancing the ability of tumor progenitor cells to transition toward SCLC.
journal_name
Oncogenejournal_title
Oncogeneauthors
Kalari S,Jung M,Kernstine KH,Takahashi T,Pfeifer GPdoi
10.1038/onc.2012.362subject
Has Abstractpub_date
2013-07-25 00:00:00pages
3559-68issue
30eissn
0950-9232issn
1476-5594pii
onc2012362journal_volume
32pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Defects in a developmental signaling pathway involving the mammalian homologue of the Drosophila segment polarity gene, patched are associated with human tumors such as basal cell carcinoma, medulloblastoma and squamous cell carcinoma. Loss of heterozygosity (LOH) in some of these tumor cells suggests that patched fun...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205370
更新日期:2002-04-18 00:00:00
abstract::Histone deacetylases (HDACs) negatively regulate gene expression by removing acetyl groups from lysine residues present in histones and other proteins. Histone deacetylase 3 is unique among the Class I family of HDACs, as it is able to shuttle between the nucleus and the cytoplasm, whereas the other family members rem...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209473
更新日期:2006-07-27 00:00:00
abstract::This issue attempts to give a 'state of the art' overview of the AP-1 transcription factor family, a fundamental class of transcriptional regulators. The AP-1 family consists of several bZIP (basic region leucine zipper) domain proteins, the Jun, the Fos, and the ATF subfamilies, which all have to dimerize before they...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204416
更新日期:2001-04-30 00:00:00
abstract::BRCA1 mutation carriers have an increased susceptibility to breast and ovarian cancer. Excision of exon 11 of Brca1 in the mouse, using a conditional knockout (Cre-loxP) approach, results in mammary tumor formation after long latency. To characterize the genomic instability observed in these tumors, to establish a com...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205636
更新日期:2002-08-01 00:00:00
abstract::The tumor suppressor gene Pdcd4 (programmed cell death gene 4) has drawn considerable attention because its downregulation is involved in the development of several types of cancer. Because Pdcd4 interacts with the translation initiation factor eIF4A and inhibits its helicase activity, Pdcd4 has been implicated in the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.83
更新日期:2015-03-12 00:00:00
abstract::The Ewing sarcoma is the second most common bone tumor in children and young adults. Despite the advances in therapy, the 5-year survival rate for patients with metastatic disease is poor, indicating the need for alternative treatments. Here, we report that 2-methoxy-estradiol (2-Me), a natural estrogen metabolite, in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206356
更新日期:2003-05-01 00:00:00
abstract::Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine wheth...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200203
更新日期:1998-04-30 00:00:00
abstract::Pax3 is an evolutionarily conserved transcription factor that plays a major role in a variety of developmental processes. Mutations in Pax3 lead to severe malformations as seen in human Waardenburg syndrome and in the Splotch mutant mice. The transcriptional activity of Pax3 was recently shown to be repressed by Daxx ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204063
更新日期:2001-01-04 00:00:00
abstract::Knowledge of tumour initiation in human epithelia is limited by sample availability and difficulty in experimental manipulation of human cells. The thyroid is a useful model since, in addition to multiple tumour stages, it presents two distinct 'pathways' of tumorigenesis: 'follicular' tumours, in which ras oncogene m...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Nerve growth factor induces differentiation and survival of rat PC12 pheochromocytoma cells. The activation of the erk cascade has been implicated in transducing the multitude of signals induced by NGF. In order to explore the role of this signaling cascade in NGF mediated survival, differentiation and proliferation, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202524
更新日期:1999-03-25 00:00:00
abstract::Although apoptosis can be induced by the enforced expression of exogenously introduced c-myc genes, it is not clear whether overexpression resulting from the amplification of the resident c-myc gene in tumor cells is sufficient to induce apoptosis. We have investigated the relationship between c-myc gene amplification...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202309
更新日期:1999-01-14 00:00:00
abstract::Homeobox genes encode transcription factors that are essential for normal development and are often dysregulated in cancers. The molecular mechanisms that cause their misregulation in cancers are largely unknown. In this study, we investigate the mechanism by which the Six1 homeobox protein, which has a crucial role d...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.233
更新日期:2010-09-02 00:00:00
abstract::MicroRNAs (miRNAs) as modulators of gene expression have been described to display both tumor-promoting and tumor-suppressive functions. Although their role has been studied in different tumor types, little is known about how they regulate nuclear factor κB (NF-κB) signaling in breast cancer. Here, we performed an unb...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.571
更新日期:2012-09-13 00:00:00
abstract::The eph gene encodes a putative receptor tyrosine kinase for an as yet unknown ligand. Some human cancer cells have been found to overexpress eph mRNAs without gene amplification. We show here that NIH3T3 cells acquire tumorigenic ability in nude mice and make colonies in soft agar with a viral LTR (Long Terminal Repe...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Chromosome 17 is one of the most frequently altered chromosomes in malignant breast cancer. At least four genes implicated in breast cancer reside on chromosome 17 (p53, 17p13; Her-2/neu/ERBB2, 17q12; BRCA1, 17q21; and nm23, 17q22). In addition, allelic imbalance has been described for at least five regions of chromos...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201073
更新日期:1997-05-15 00:00:00
abstract::Transcription from the rat TGF alpha promoter initiates at two predominant sites (-188 and -58) in a G+C-rich region that does not contain TATA or CAAT motifs. Previous studies using transfected reporter constructs implicated the transcription factor Sp1 in active expression from the promoter, particularly from the -5...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Amplified segments of the long arm of chromosome 12 are frequently observed in human sarcomas. In most cases there are separate amplified regions around the MDM2 and CDK4 genes. Here we show recurrent amplification of a third region encompassing HMGIC, a human architectural transcription factor gene. Reduced amplifica...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201135
更新日期:1997-06-19 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal human cancers, with 5-year patient survival rates of <5%. Activating mutations in KRAS are the predominant oncogenic drivers of PDAC but are accompanied by additional lower frequency genetic alterations. Our group previously identified the guanine ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0985-1
更新日期:2020-01-01 00:00:00
abstract::Centromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.508
更新日期:2011-03-17 00:00:00
abstract::The maintenance cytosine DNA methyltransferase DNMT1 and de novo methyltransferase DNMT3b cooperate to establish aberrant DNA methylation and chromatin complexes to repress gene transcription during cancer development. The expression of DNMT3b was constitutively increased 5-20-fold in hTERT/CDK4-immortalized human bro...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.580
更新日期:2015-01-29 00:00:00
abstract::Osteochondroma, the most common benign bone tumor, may occur as a sporadic lesion or as multiple neoplasms in the context of multiple osteochondromas syndrome. The most severe complication is malignant transformation into peripheral secondary chondrosarcoma. Although both benign conditions have been linked to defects ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.135
更新日期:2010-07-01 00:00:00
abstract::Steroid receptor co-activator-3 (SRC-3/AIB1) is an oncogene that is amplified and overexpressed in many human cancers. However, the molecular mechanisms that regulate 'activated SRC-3 oncoprotein' turnover during tumorigenesis remain to be elucidated. Here, we report that speckle-type POZ protein (SPOP), a cullin 3 (C...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.151
更新日期:2011-10-20 00:00:00
abstract::Expression level of metastasis-associated protein 1 (MTA1) is closely related to tumor growth and metastasis in various cancers. Although increased expression level of MTA1 was observed in hepatocellular carcinoma (HCC), role of MTA1 complex containing histone deacetylase (HDAC) in hepatitis B virus (HBV)-associated h...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211000
更新日期:2008-05-29 00:00:00
abstract::Tat protein is an early nonstructural protein necessary for virus replication, which is secreted by infected cells and taken up by uninfected cells. Extensive evidence indicates that Tat may be a cofactor in the development of AIDS-related neoplasms. The molecular mechanism underlying Tat's oncogenic activity may incl...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206637
更新日期:2003-09-18 00:00:00
abstract::p8 is a stress-induced DNA-binding protein, biochemically related to the architectural chromatin binding HMG protein family and whose function is presently unknown. We obtained fibroblast from mice lacking p8 and found that p8 is involved in cell growth regulation and in apoptosis. p8(-/-) mouse embryonic fibroblasts ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205222
更新日期:2002-03-07 00:00:00
abstract::Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin-angiotensin system (RAS) is a major physiological regulatory pathway controlling salt-water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are media...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0563-y
更新日期:2019-03-01 00:00:00
abstract::O-linked glycans of secreted and membrane-bound proteins have an important role in the pathogenesis of pancreatic cancer by modulating immune responses, inflammation and tumorigenesis. A critical aspect of O-glycosylation, the position at which proteins are glycosylated with N-acetyl-galactosamine on serine and threon...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.194
更新日期:2011-12-08 00:00:00
abstract::DSS1 is an evolutionarily conserved acidic protein that binds to BRCA2. However, study of the function of DSS1 in mammalian cells has been hampered because endogenous DSS1 has not been detectable by Western blotting. Here, we developed a modified Western blotting protocol that detects endogenous DSS1 protein, and used...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209153
更新日期:2006-02-23 00:00:00
abstract::The E2F1 transcription factor plays a pivotal role in driving cells out of a quiescent state and into the S phase of the cell cycle, in part by transactivating genes needed for DNA replication including DHFR, thymidine kinase, and DNA Polymerase alpha. E2F1 has also been implicated in regulating an S phase checkpoint,...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205473
更新日期:2002-05-23 00:00:00
abstract::The DCC (deleted in colorectal cancer) gene was originally identified as a candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may also be ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-08-15 00:00:00