Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fine needle aspiration Biopsy (FNAB) is commonly used to diagnose thyroid tumors. In some clinical situations, however, accurate diagnosis requires a more objective method than cytological examination alone. Medullary thyroid carcinomas (MTC) derive from C cells in the thyroid and express some specific messenger RNAs (mRNA), such as those transcribed from the RET proto-oncogene, the calcitonin gene, and the gene for carcinoembryonic antigen (CEA), which usually do not exist in normal thyroid follicular cells or thyroid tumors of follicular epithelial descent. Recently, we established a new method for the molecular diagnosis of thyroid tumors without additional invasion to the patient by extracting RNA for RT-PCR from the leftover cells inside the needles used for fine needle aspiration biopsy (Aspiration Biopsy-Reverse Transcription-Polymerase Chain Reaction, ABRP). By applying the ABRP method to the detection of RET, calcitonin, and CEA mRNAs, an accurate molecular-based diagnosis for MTC maybe established as an adjunct to cytological diagnosis. In this study, 35 aspirates were obtained at the time of surgery from thyroid tumors, including 11 MTCs. The expression of these mRNAs in the leftover cells inside the needles used for the aspiration was then examined. Transcripts from all three genes were detected in the samples from all 11 MTCs, but none of these mRNAs were detected in the other tumors or normal thyroid tissues. Furthermore, MTC was preoperatively diagnosed in three patients by ABRP detection of these mRNAs, and these diagnoses were confirmed by subsequent cytological and histopathological analyses. Thus RT-PCR detection of RET, calcitonin, and CEA mRNAs in FNABs may be an efficient molecular adjunct for diagnosing MTC.
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PMID:Preoperative diagnosis of medullary thyroid carcinoma by RT-PCR using RNA extracted from leftover cells within a needle used for fine needle aspiration biopsy. 1008 77

The authors performed a prospective study evaluating molecular diagnosis in patients with bilateral coronal synostosis. The patients were divided into two groups: (1) those clinically classified as having Apert, Crouzon, or Pfeiffer syndrome and (2) those clinically unclassified and labeled as having brachycephaly. Blood samples were drawn for genomic DNA analysis from 57 patients from 1995 to 1997. Polymerase chain reactions were performed using primers flanking exons in FGFR 1, 2, and 3. Each exon was screened for mutations using single-strand confirmation polymorphism, and mutations were identified by DNA sequencing. Mutations in FGFR2 or FGFR3 were found in all patients (n = 38) assigned a phenotypic (eponymous) diagnosis. All Apert syndrome patients (n = 13) carried one of the two known point mutations in exon 7 of FGFR2 (Ser252Trp and Pro253Arg). Twenty-five patients were diagnosed as having either Crouzon or Pfeiffer syndrome. Five patients with Crouzon syndrome of variable severity had mutations in exon 7 of FGFR2. Fifteen patients (12 with Crouzon, 3 with Pfeiffer) had a mutation in exon 9 of FGFR2, many of which involved loss or gain of a cysteine residue. A wide phenotypic range was observed in patients with identical mutations, including those involving cysteine. Two patients labeled as having Crouzon syndrome had the Pro250Arg mutation in exon 7 of FGFR3. All three patients with the crouzonoid phenotype and acanthosis nigricans had the same mutation in exon 10 of FGFR3 (Ala391Glu). This is a distinct disorder, characterized by jugular foraminal stenosis, Chiari I anomaly, and intracranial venous hypertension. Mutations were found in 14 of 19 clinically unclassifiable patients. Three mutations were in exon 9, and one was in the donor splice site of intron 9 on FGFR2. The most common mutation discovered in this group was Pro250Arg in exon 7 of FGFR3. These patients (n = 10) had either bilateral or unilateral coronal synostosis, minimal midfacial hypoplasia with class I or class II occlusion, and minor brachysyndactyly. No mutations in FGFR 1, 2, or 3 were detected in five patients with nonspecific brachycephaly. In conclusion, a molecular diagnosis was possible in all patients (n = 38) given a phenotypic (eponymous) diagnosis. Different phenotypes observed with identical mutations probably resulted from modulation by their genetic background. A molecular diagnosis was made in 74 percent of the 19 unclassified patients in this series; all mutations were in FGFR2 or FGFR3. Our data and those of other investigators suggest that we should begin integrating molecular diagnosis with phenotypic diagnosis of craniosynostoses in studies of natural history and dysmorphology and in analyses of surgical results.
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PMID:Molecular diagnosis of bilateral coronal synostosis. 1054 Nov 59

We describe the clinicopathologic, immunophenotypic, and molecular findings in 4 cases of anaplastic large cell lymphoma (ALCL) arising in the small intestine. All patients were men with acute symptoms of gastrointestinal tract obstruction. The clinical preoperative diagnosis was gastrointestinal carcinoma in 3 cases, and pancreatic carcinoma in 1 case. Histologic examination revealed cohesive aggregates of neoplastic cells, with multiple vesicular nuclei, prominent nucleoli, and abundant amphophilic cytoplasm. There was no clinical or histopathologic evidence of enteropathy. All cases were CD30+, and all showed evidence of T-cell lineage with cytotoxic potential by expression of CD3, CD43, or CD45RO; T-cell intracellular antigen-1; or perforin. One tumor showed p80 and anaplastic lymphoma kinase (ALK) overexpression corroborated by the presence of the t(2:5). One tumor expressed Epstein-Barr virus latent membrane protein. In all cases, the tumor cells were negative for CD20, CD15, CD56, and cytokeratin. Polymerase chain reaction revealed clonal rearrangements of the T-cell receptor gamma-chain gene, without evidence of immunoglobulin heavy-chain gene rearrangement. The diagnosis of primary bowel ALCL is facilitated by immunophenotypic and molecular studies. With 24 months of clinical follow-up, only the patient with the t(2:5)-positive tumor is alive and free of disease, suggesting that p80/ALK overexpression may be a good prognostic indicator.
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PMID:Primary anaplastic large cell lymphoma of the small intestine. 1076 69

Polymerase chain reaction-restriction fragment length polymorphism based genotyping assays were used to determine the frequency of polymorphisms in CYP1A1 (3'-flanking region), CYP2E1 (5'-flanking region and intron 6), EPHX (exon 3 and exon 4), GSTM1 (deletion), GSTP1 (exon 5) and GSTT1 (deletion) in a group of 416 Czech individuals. A comprehensive overview of the methodology is also presented. We have found the following frequencies of mutated alleles: CYP1A1-m2, 0.097; CYP2E1-C, 0.077; CYP2E1-c2, 0.023; EPHX(exon 3)-His, 0.381; EPHX(exon 4)-Arg, 0.198; GSTM1-null, 0.51; GSTP1-Val, 0.3; GSTT1-null, 0.164. These values are similar to those presented in the majority of studies on European Caucasians, although a few cases of significant differences in the distribution of genotypes were found. These differences were most probably caused by methodological variations or statistical bias in the analyses of low numbers of samples in the control groups of some authors. Based on the results of EPHX genotyping, the activity of its protein product was deduced and the Czech population was divided into three subgroups with low, medium and high EPHX activity. We found that 43% of the Czech population would fall into the low, 44% into the medium and 13% into the high EPHX activity group. The data obtained may prove to be very useful for epidemiological studies on the influence of genetic polymorphisms of biotransformation enzymes on carcinogenesis or other environment-related diseases.
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PMID:Genetic polymorphisms of biotransformation enzymes: allele frequencies in the population of the Czech Republic. 1119 82

RET fused gene (RFG)/ELE1alpha/androgen receptor-associated protein 70(ARA70) was first found to be involved in the activation of the RET proto-oncogene in thyroid neoplasm and has recently been shown to be a ligand-dependent transcriptional coregulator for androgen receptor (AR). The functionality of RFG/ELE1alpha/ARA70 remains controversial, and little is known about factors regulating its expression in the prostate. Of significant interest is whether this molecule is involved in prostate carcinogenesis. Using reverse transcriptase-polymerase chain reaction semiquantitation, we compared RFG/ELE1alpha/ARA70 mRNA levels in four prostate cancer cell lines (LNCaP, TSU-Pr1, DU-145, and PC-3) with those found in primary cultures of normal prostatic epithelial cells (PrECs). In addition, we examined the effects of androgen and antiandrogen, estrogen and antiestrogen, and a demethylating agent on RFG/ELE1alpha/ARA70 mRNA expression levels in AR- and AR+ PC-3 cells. Reduced levels of RFG/ELE1alpha/ARA70 message were observed in all four prostate cancer cell lines when compared with normal PrECs in primary cultures. RFG/ELE1alpha/ARA70 mRNA levels in PC-3 cells, which express both estrogen receptor subtypes, were upregulated by 17beta-estradiol and inhibited by the antiestrogen ICI-182780. In PC-3(AR+) cells, which were genetically engineered to express AR, exposure to androgen upregulated RFG/ELE1alpha/ARA70 mRNA expression, whereas treatment with 4-hydroxyflutamide lowered expression of this transcript. Furthermore, treatment of DU-145 cells, which did not express RFG/ELE1alpha/ARA70 transcripts, with a demethylating agent reactivated transcription of this gene. Polymerase chain reaction analyses of monochromosomal human-rodent hybrid panels localized a putative RFG/ELE1alpha/ARA70 isoform on human chromosome 5q31.1-31.2. In summary, we identified sex hormones and DNA hypermethylation as regulators of RFG/ELE1alpha/ARA70 expression in prostate cancer cells. In addition, we found reduced levels of RFG/ELE1alpha/ARA70 expression in prostate cancer cell lines when compared with expression levels in normal PrECs in culture. These findings suggest that RFG/ELE1alpha/ARA70 may be involved prostate carcinogenesis and that it may serve as a key mediator of estrogen-androgen synergism.
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PMID:Expression of RFG/ELE1alpha/ARA70 in normal and malignant prostatic epithelial cell cultures and lines: regulation by methylation and sex steroids. 1125 59

The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions and single-stranded conformational polymorphism analyses were used to examine 140 elderly AML patients enrolled in the Southwest Oncology Group study 9031 for FLT3, RAS, and TP53 mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the FLT3 (46 of 47) mutations were internal tandem duplications (ITDs) within exons 11 and 12. In the remaining case, a novel internal tandem triplication was found in exon 11. FLT3 ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All RAS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marrow blast percentages. Only 2 of 47 patients with FLT3 ITDs also had a RAS mutation, indicating a significant negative association between FLT3 and RAS mutations (P =.0013). Most TP53 mutations (11 of 12) were missense point mutations in exons 5 to 8 and were associated with abnormal cytogenetics, especially abnormalities in both chromosomes 5 and 7. FLT3 and RAS mutations were not associated with inferior clinical outcomes, but TP53 mutations were associated with a worse overall survival (median 1 versus 8 months, P =.0007). These results indicate that mutations in FLT3, RAS, or TP53 are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes. (Blood. 2001;97:3589-3595)
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PMID:FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. 1136 55

Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.
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PMID:Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum. 1147 65

Most post transplantation lymphoproliferative disorders (PTLDs) are Epstein-Barr virus (EBV) associated B cell proliferations. We report a case of aggressive anaplastic large cell lymphoma expressing the anaplastic lymphoma kinase (ALK) protein in a 58 year old man who had previously undergone liver transplantation. A definite diagnosis was not possible on histopathological examination. Immunostaining clearly showed a predominant population of small irregular lymphocytes, admixed with large cells strongly positive for CD30, epithelial membrane antigen, and the ALK protein. Neoplastic cells were of the T/cytotoxic phenotype. In situ hybridisation with EBV encoded early RNA probes showed only a few scattered positive non-neoplastic small lymphocytes. Polymerase chain reaction analysis of immunoglobulin and T cell receptor rearrangements was negative. The NPM-ALK fusion transcript associated with the t(2;5) translocation was detected by reverse transcription polymerase chain reaction. A review of the literature revealed 76 cases of T cell PTLD, showing a broad spectrum of morphological features and clinical behaviour. Most of these cases were EBV negative (61 of 76) and occurred after renal transplantation (48 of 76). To our knowledge, this is the first case of ALK positive lymphoma occurring in the setting of organ transplantation. This observation stresses the need for accurate immunostaining for diagnosing this rare, apparently aggressive, lymphoma in immunosuppressed patients.
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PMID:Anaplastic lymphoma kinase (ALK) protein expressing lymphoma after liver transplantation: case report and literature review. 1240 29

HER2-positive status is the sole criterion for identifying patients with breast cancer for Herceptin therapy, which has known efficacy in women with metastatic breast cancer (MBC). Immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), which measure the HER2 protein and gene, respectively, are currently the most widely used HER2 tests in the clinical setting. However, results from these assays are influenced by many variables including choice of antibody or probe, methodology, level of user experience and interlaboratory variability. Although there is no widespread standard testing algorithm, the importance of HER2 in clinical practice demands accurate and reproducible tests. Polymerase chain reaction (PCR) and chromogenic in-situ hybridization (CISH) represent upcoming methods for assessing HER2 gene amplification. Enzyme-linked immunosorption assay (ELISA), a semi-automated technique that can be used to measure the level of the HER2 extracellular domain (ECD) in serum, may also prove useful. While such technologies show great promise, they will at least have to be validated against IHC or FISH before being accepted into routine clinical practice.
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PMID:Emerging technologies for HER2 testing. 1242 53

To clarify the pathogenesis of Hirschsprung's disease (HD) on molecular level and to reveal the relationship between the RET proto-oncogene and Chinese patients with HD, the mutations of the RET proto-oncogene were studied in 50 Chinese patients with HD and 30 normal children with an obstipation as control. Genomic DNA was extracted from venous blood of the HD patients and the normal children. Polymerase chain reaction (PCR) products, which were amplified using specific primers (RET; exon13), were electrophoresised to analyze the single-strand conformational polymorphism (SSCP) patterns. DNA sequences of exon 13 of the RET proto-oncogene were determined in patients showing abnormal SSCP bands. And then the familial tracking research was done for the patients with Exon 13 mutation. In 50 HD patients, seven cases were found with apparently abnormal SSCP bands. And three point mutations were proved by DNA sequencing. In the parents of seven HD patients with Exon 13 mutation, two patients' fathers had the same mutation as their children. The results suggest that the mutation of the RET proto-oncogene may have a high freqency in Chinese patients with HD, especially the heterozygous point mutation. And HD has the heredity tendency.
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PMID:[The mutation character of the RET proto-oncogene in Chinese patients with Hirschsprung's disease]. 1457 88


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