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Journal of Clinical Pathology Apr 1992To see if the relative expressions of proto-oncogenes that are increased in acute myeloid leukaemia are raised in patients with myelodysplastic syndromes (MDS), and to...
AIMS
To see if the relative expressions of proto-oncogenes that are increased in acute myeloid leukaemia are raised in patients with myelodysplastic syndromes (MDS), and to see if they increase with progression to leukaemia. To note if there is a correlation between morphology, karyotype, and these proto-oncogene expressions and if any one proto-oncogene can predict prognosis.
METHOD
Bone marrow from 130 patients was analysed at six monthly intervals over two years for relative mRNA expression of seven oncogenes, karyotype, and morphology. The technique used slot blot hybridisation and densitometric analysis. The results were compared with 14 surgical controls and 30 people with vitamin deficiency anaemia.
RESULTS
Six of seven oncogenes showed increased expression which progressed with time, but did not correlate with morphological or karyotypic changes. Expression of four of the seven oncogenes was increased in megaloblastic and iron deficiency anaemia. C-mos showed differences among the five morphological subgroups; it correlated with abnormal location (p = 0.025) and seemed to influence prognosis.
CONCLUSION
Increased proto-oncogenes reflect the overall marrow perturbation in MDS. C-mos may reflect persistence of monocyte pathway which confirms marrow stability.
Topics: Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Megaloblastic; Chromosome Aberrations; Chromosome Disorders; Female; Follow-Up Studies; Gene Expression; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Proto-Oncogene Mas; Proto-Oncogenes
PubMed: 1577972
DOI: 10.1136/jcp.45.4.339 -
Cancer Sep 2017Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival...
BACKGROUND
Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC.
METHODS
Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical pathway mutations and relapse-free survival (RFS) and overall survival were analyzed. The associations were further analyzed according to the tumor location.
RESULTS
The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-β pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52). Proximal tumors showed a higher mutation rate than distal tumors, and the mutation profile was different according to the tumor location. The mutation rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), and B-Raf proto-oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The better RFS with the PI3K pathway mutation was significant only for proximal tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only for distal tumors.
CONCLUSIONS
A PI3K pathway mutation was associated with better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK-RAS pathway mutation was associated with worse RFS. The significance of the prognostic impact differed according to the tumor location. Cancer 2017;123:3513-23. © 2017 American Cancer Society.
Topics: Adult; Aged; Chemotherapy, Adjuvant; Class I Phosphatidylinositol 3-Kinases; Cohort Studies; Colectomy; Colorectal Neoplasms; Combined Modality Therapy; Confidence Intervals; Critical Pathways; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Genes, ras; Humans; Male; Middle Aged; Mutation; Odds Ratio; Predictive Value of Tests; Prognosis; Proto-Oncogene Mas; Proto-Oncogenes; Republic of Korea; Retrospective Studies; Survival Analysis; Treatment Outcome
PubMed: 28513830
DOI: 10.1002/cncr.30760 -
Japanese Journal of Cancer Research :... Apr 1994HCS-2/8 is a stable human chondrosarcoma cell line with many chondrocytic characteristics and has the capacity to form chondrosarcomas in nude mice. The cells display...
HCS-2/8 is a stable human chondrosarcoma cell line with many chondrocytic characteristics and has the capacity to form chondrosarcomas in nude mice. The cells display both biochemically and morphologically definable changes in sparse, subconfluent, confluent and over-confluent phases of in vitro culture. Such features of HCS-2/8 cells may reflect the processes of both proliferation and differentiation of chondrocytes in vivo. We examined the correlations of these changes of HCS-2/8 cells with their transcript levels of 21 proto-oncogenes by Northern analysis. We found no detectable transcripts of 9 proto-oncogenes (c-sis, c-met, c-src, c-lyn, c-fgr, c-ros, c-pim, Blym and N-myc), but detected transcripts of 12 other proto-oncogenes (int-2, erbB, c-abl, c-raf-1, c-fyn, K-ras, H-ras, c-mos, c-myc, c-myb, c-fos, and c-jun). In the over-confluent phase, the levels of c-fos and c-raf-1 were increased several dozen times and about 5 times, respectively, while the level of c-abl was about 1/5th of that in the sparse, subconfluent and confluent phases of culture. The level of int-2 increased about 10-fold in the confluent and over-confluent phases of in vitro culture. The transcript levels of c-mos and K-ras were high in the sparse phase, low in the subconfluent and confluent phases and high in the over-confluent phase. The levels of the other 6 proto-oncogenes in HCS-2/8 cells were constant in all phases of in vitro culture.
Topics: Chondrosarcoma; Gene Expression; Humans; Proteoglycans; Proto-Oncogene Mas; Proto-Oncogenes; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured
PubMed: 8200849
DOI: 10.1111/j.1349-7006.1994.tb02368.x -
Genes & Development Dec 1990
Review
Topics: Animals; Cell Differentiation; Cell Division; DNA-Binding Proteins; Genes, myc; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myb; Proto-Oncogene Proteins c-myc; Proto-Oncogenes
PubMed: 2279697
DOI: 10.1101/gad.4.12b.2235 -
Genes & Development Dec 1990
Review
Topics: Amino Acid Sequence; Animals; DNA Replication; Gene Expression Regulation; Genes, myc; Humans; Molecular Sequence Data; Oncogenes; Proto-Oncogene Proteins c-myc; Proto-Oncogenes; Sequence Homology, Nucleic Acid
PubMed: 2269425
DOI: 10.1101/gad.4.12a.2025 -
The International Journal of... Aug 1997Xenopus XI-ets-1 and XI-ets-2 are maternally expressed. From late oogenesis to early embryogenesis their transcripts are localized to the animal pole and the...
Xenopus XI-ets-1 and XI-ets-2 are maternally expressed. From late oogenesis to early embryogenesis their transcripts are localized to the animal pole and the intermediate zone, suggesting a function in the differentiation of animal blastomeres and future mesoderm. Their presence at the level of germ plasm suggests also a role in the differentiation of the germinal lineage. Both zygotic genes are expressed ubiquitously beginning at MBT, and then restricted to a circumblastoporal collar. In neurula and tailbud stages, ets-1 and ets-2 transcripts are detected in neural crest cells and their derivatives. Specific transcription can also be observed for ets-1 in the hemangioblastic precursors, in endothelial cells of the forming heart and blood vessels. Ets-2 is itself specifically expressed in the putative pronephros and in the forming pronephric tubules and extending pronephric duct. Like another member of the ets-gene family (XI-fli), both genes are transcribed in regions of the embryo undergoing important morphogenetic modifications, especially in migrating cells and/or along their migration pathways. We postulate that these genes orchestrate modifications of cellular adhesion. Changes in the expression of cadherins and integrins repertories would be consistent with such a role and could account for the phenotypes we reported earlier for XI-fli overexpression. Such a role would be critical for tumor cell dissemination, in addition to the one already ascribed to ets-1 in the expression of proteases specific for the extracellular matrix.
Topics: Animals; Cell Differentiation; DNA Probes; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; In Situ Hybridization; Molecular Sequence Data; Morphogenesis; Oocytes; Oogenesis; Polymerase Chain Reaction; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ets; Proto-Oncogenes; RNA, Messenger; Transcription Factors; Xenopus laevis; Zygote
PubMed: 9303349
DOI: No ID Found -
Annals of Oncology : Official Journal... May 1994
Topics: Apoptosis; Humans; Neoplasms; Prognosis; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogenes
PubMed: 8075043
DOI: No ID Found -
Mechanisms of Development Mar 2000The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from cell surface receptors to the...
The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from cell surface receptors to the nucleus. In vertebrates, Raf signaling has been implicated in the progression of mouse embryos through the two-cell stage and in the induction of posterior mesoderm. However, mouse embryos mutant for each of the Raf genes exhibit no developmental defects before mid-gestation. Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles. Our results show that Raf signaling is indeed indispensable for normal development beyond the blastocyst stage. However, due to a significant redundancy between Craf-1 and Braf, either gene is sufficient for normal development until mid-gestation. The molecular and developmental mechanisms for this redundancy were investigated by monitoring the expression of Raf genes throughout embryogenesis and by biochemical studies in mutant cell lines.
Topics: Animals; Cells, Cultured; Embryonic and Fetal Development; Gene Expression Regulation, Developmental; Isoenzymes; Mice; Mutagenesis; Phenotype; Proto-Oncogene Proteins c-raf; Proto-Oncogenes
PubMed: 10704835
DOI: 10.1016/s0925-4773(99)00276-2 -
Nature Genetics Jun 2018Widespread mRNA 3' UTR shortening through alternative polyadenylation promotes tumor growth in vivo . A prevailing hypothesis is that it induces proto-oncogene...
Widespread mRNA 3' UTR shortening through alternative polyadenylation promotes tumor growth in vivo . A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3'UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3' UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3' UTR shortening, including PTEN, a crucial tumor-suppressor gene involved in ceRNA crosstalk with nine 3'UTR-shortening genes, including EPS15 and NFIA. Knockdown of NUDT21, a master 3' UTR-shortening regulator , represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3' UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis.
Topics: 3' Untranslated Regions; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; HeLa Cells; Humans; MCF-7 Cells; MicroRNAs; Neoplasms; Proto-Oncogene Mas; Proto-Oncogenes; RNA; RNA, Messenger
PubMed: 29785014
DOI: 10.1038/s41588-018-0118-8 -
Scientific Reports Jan 2024Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived...
Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit. Interestingly, all of these cases showed only trkB but not trkA/trkC expression. Cap analysis of gene expression (CAGE) analysis identified increased number of genes whose promoters were activated in pan-trk/trkB positive GISTs. Imbalanced expression of NTRK2, which suggests the presence of NTRK2 fusion, was not observed in any of trkB positive GISTs, despite higher mRNA expression. TrkB expression was found in duodenal GISTs and more than half of small intestinal GISTs, and this subset of cases showed poor prognosis. However, there was not clear difference in clinical outcomes according to the trkB expression status in small intestinal GISTs. These findings may provide a possible hypothesis for trkB overexpression contributing to the tumorigenesis and aggressive clinical outcome in GISTs of duodenal origin.
Topics: Humans; Gastrointestinal Stromal Tumors; Prognosis; Receptor Protein-Tyrosine Kinases; Proto-Oncogenes; Proto-Oncogene Proteins c-kit
PubMed: 38191907
DOI: 10.1038/s41598-024-51211-7