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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preliminary studies of RAS mutational activation in human testicular germ cell neoplasms have yielded conflicting results. Whereas two studies of clinical material revealed a significant incidence of N- and KRAS mutations, two studies of a variety of germ cell lines failed to document RAS mutations. To clarify the incidence of RAS mutations in these tumors, we studied archival paraffin-embedded, formalin-fixed orchiectomy specimens from 25 nonseminomas (NSGCT), 18 seminomas (SEM), and one Leydig cell tumor. For 14 of the 44 neoplasms, DNA was also available from nonmalignant testis adjacent to the tumor. Six age-matched patients had testes removed because of nonmalignant disease and were studied as controls. Polymerase chain reaction (PCR) amplified the K-, N-, and HRAS 12, 13, and 61 codons of these specimens, and mutations were detected with mutation-specific oligonucleotide probe hybridization of Southern and slot blots. Four mutations were found in KRAS 12 (4/44;[9.1%]). One seminoma [1/18(5.6%)] contained the mutation GGT(GLY)----CGT(ARG), and three NSGCT [3/25(12%)] were found to have GGT(GLY)----GAT(ASP) mutations. One of the NSGCT mutations was detected in adjacent nonmalignant tissue, but the corresponding tumor did not contain any detectable mutation. No mutations were detected at KRAS 13 or 61, in NRAS or HRAS 12, 13, or 61, or in the control normal testes. PCR, slot blots, and hybridizations were performed twice by two separate investigators for confirmation of results. PCR-generated mutation-specific positive controls were created for all possible RAS mutations, and these along with wild-type DNA controls were integral to interpretation of the oligonucleotide mismatch hybridization assay. By using positive and negative controls, we have detected a relatively low incidence of RAS mutations in archival human testicular germ cell tumors.
Genes Chromosomes Cancer 1992 Sep
PMID:Detection of RAS mutations in archival testicular germ cell tumors by polymerase chain reaction and oligonucleotide hybridization. 138 46

We have studied 31 male germ cell tumors (GCTs) for probable mutations in codons 12, 13, and 61 of HRAS, KRAS, and NRAS oncogenes using the polymerase chain reaction. Twenty of the thirty-one tumors exhibited NRAS gene mutations, 14 in codon 61, and six in codon 12, whereas no mutations were detected in HRAS and KRAS genes. The NRAS mutations were equally prevalent in seminomatous and nonseminomatous GCTs. Thus 13 of 22 seminomas, six of seven embryonal carcinomas, and one of two mixed tumors exhibited mutations. Two non-seminomatous tumors (an embryonal carcinoma and a yolk sac/teratoma) had mutations in both codons 12 and 61. The high frequency of NRAS mutations observed in the present study suggests that NRAS gene products may play an important role in growth regulatory functions of premalignant and malignant germ cells.
Genes Chromosomes Cancer 1990 Jan
PMID:Detection of preferential NRAS mutations in human male germ cell tumors by the polymerase chain reaction. 196 83

RAS protooncogene activation has been repeatedly demonstrated in neoplastic cell DNA from patients with AML. Despite the convincing demonstration that activating RAS gene point mutations are critical in model systems, their precise prevalence and importance in human cancers such as AML remain speculative. The technology for identifying RAS mutations has changed considerably in recent years. We examined a prospective cohort of 43 acute myeloid leukemia (AML) patients admitted to the University of Maryland Cancer Center for first and second exon mutations of NRAS and KRAS using PCR and DNA sequence analysis. Six (14%) 1st exon NRAS mutations were identified. No clinical or biologic parameter has yet been observed to segregate with RAS activation, although a larger study may be needed to demonstrate this.
Genes Chromosomes Cancer 1990 May
PMID:RAS gene activation in acute myelogenous leukemia: analysis by in vitro amplification and DNA base sequence determination. 227 67

Mutations at codon 12, 13, and 61 of the HRAS, KRAS, and NRAS genes were evaluated in 99 cases of pediatric acute myeloid leukemia (AML) using oligonucleotide hybridization to polymerase chain reacted derived products. Twenty-four mutations were identified in the NRAS gene, 13 in the KRAS gene, and none in the HRAS gene. The mutations occurred in a broad spectrum of cases, and there was no specific association of RAS gene mutations with patient subsets defined on the basis of clinical or hematologic features. These data demonstrate that RAS gene mutations are at least as common in childhood AML as in adult AML and suggest that RAS gene mutations play a role in myeloid neoplasia in both age groups.
Genes Chromosomes Cancer 1990 Jul
PMID:RAS gene mutations in childhood acute myeloid leukemia: a Pediatric Oncology Group study. 227 70

Expression of 16 oncogenes was investigated in a series of human meningiomas showing a normal chromosome complement or the characteristic monosomy 22 but no structural aberrations detectable by banding analysis. By dot hybridization, the only expressed sequence detected was KRAS. The expression was elevated approximately 6--8-fold in comparison to matrix tissue (meninges) and to fibroblasts of the corresponding patient. Northern blot analysis displayed the typical banding pattern and an 8--10-fold overexpression. DNA analysis did not reveal gene amplification or major rearrangements in the KRAS gene structure.
Cancer Lett 1988 Dec 01
PMID:Human KRAS oncogene expression in meningioma. 246 63

The expression of RAS oncogenes in benign and malignant salivary gland tumors was studied by immunohistochemistry and by immunoblotting using monoclonal antibodies recognizing the HRAS and KRAS gene products. Twenty-eight out of 29 benign pleomorphic adenomas overexpressed p21RAS, whereas only 12 out of 18 malignant salivary gland tumors expressed the p21 protein. The expression levels were also substantially higher in the adenomas than in the malignant tumors, indicating that RAS gene activation appears to be more frequent and of greater importance for benign than for malignant salivary gland tumors. Comparisons of the p21 expression levels with the karyotypes of the pleomorphic adenomas revealed a novel correlation between high p21 expression and chromosome 8 rearrangements. As a hypothesis, it is suggested that a novel gene located on the proximal long arm of chromosome 8, most likely at band q12, is involved in the regulation of RAS gene expression.
Genes Chromosomes Cancer 1989 Sep
PMID:High p21RAS expression levels correlate with chromosome 8 rearrangements in benign human mixed salivary gland tumors. 256 14

We investigated the frequency of mutations activating RAS oncogenes in human lymphoid malignancies, including B- and T-cell-derived acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. By the polymerase chain reaction/oligonucleotide hybridization method, DNA from 178 cases was analyzed for activating mutations involving codons 12 and 61 of the HRAS, KRAS and NRAS genes and codon 13 of the NRAS gene. Mutations involving codons 12 or 13 of the NRAS gene were detected in 6 of 33 cases of acute lymphoblastic leukemia (6/33, 18%), whereas no mutations were found in non-Hodgkin lymphoma or chronic lymphocytic leukemia. Direct nucleotide sequence analysis of polymerase chain reaction products showed that the mutations involved a G----A transition in five of the six cases of acute lymphocytic leukemia. In four cases the mutations seemed to occur in only a fraction of the neoplastic cells, and one case displayed two distinct NRAS mutations, most likely present in two distinct cell populations. These results indicate the following: (i) RAS oncogenes are not found in all types of human malignancies, (ii) significant differences in the frequency of RAS mutations can be found among subtypes of neoplasms derived from the same tissue, (iii) in lymphoid neoplasms the NRAS mutation correlates with the most undifferentiated acute lymphocytic leukemia phenotype, and (iv) NRAS mutations present in only a fraction of malignant cells may result from either the selective loss or the acquisition of mutated alleles during tumor development.
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PMID:Analysis of RAS oncogene mutations in human lymphoid malignancies. 305 5

Recently, conflicting results have been reported on the incidence of RAS mutations in primary testicular germ cell tumors of adults (TGCTs). In four studies a low incidence of mutations (less than 15%) in a variety of TGCTs or derived cell lines was found, whereas in two other studies a high incidence of N- or KRAS mutations (over 40%) was shown. A total of 62 testicular seminomas (SE) and 34 nonseminomatous TGCTs (NS) were studied thus far. The largest series consisted of 42 TGCTs, studied on paraffin embedded tissue. We present the results of analysis for the presence of N- and KRAS mutations, in codons 12, 13, and 61, in snap frozen samples of 100 primary TGCTs, comprising 40 SE and 60 NS. Using the polymerase chain reaction (PCR) and allele specific oligonucleotide hybridization (ASO), mutations were found in five SE (three in NRAS and two in KRAS, all codon 12), and in one NS (KRAS, codon 12). To exclude underestimation of the incidence of RAS mutations in TGCTs due to the presence of an excess of wild type alleles in the analyzed sample, a PCR technique preferentially amplifying KRAS alleles with a mutation in codon 12 was applied to all SE. This approach, allowing a 250 times more sensitive assay, resulted in the detection of only one additional SE with a mutation. Based on a critical analysis of published data and on our results from the largest series of frozen samples investigated thus far, we conclude that N- or KRAS mutations are rare and apparently not essential for initiation or progression of TGCTs.
Genes Chromosomes Cancer 1995 Feb
PMID:N- and KRAS mutations in primary testicular germ cell tumors: incidence and possible biological implications. 753 83

Numerous molecular genetic events occurring in the development of sporadic colorectal neoplasia have been previously defined. The most frequent genetic alterations are mutations of the APC, KRAS, and TP53 genes, as well as loss of the DCC gene and of the second TP53 allele. The data from several groups indicate that these genes play an important role in ulcerative colitis-associated dysplasias and cancer, as they do in sporadic colorectal adenomas and carcinomas. KRAS and TP53 mutations were detected in dysplasia, but also in villous regeneration and active colitis, and affect a subpopulation of the cells composing these lesions. We conclude that in histologically defined dysplasia, clones can be found that genetically represent precancerous lesions in ulcerative colitis. Seen in this way, part of the active colitis and villous regeneration lesions might be considered as preneoplastic. When present, KRAS mutation is an excellent genetic marker to map populations of preneoplastic cells.
Eur J Cancer
PMID:Molecular genetics of dysplasia in ulcerative colitis. 757 15

Children with neurofibromatosis, type 1 (NF-1) are at increased risk of developing malignant myeloid disorders and their bone marrows frequently show loss of the normal allele of the NF1 tumor-suppressor gene. NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. We used a genetic approach to test the hypothesis that NF1 negatively regulates myeloid cell growth through its effect on Ras. This model predicts that, if RAS mutations and loss of NF1 function deregulate myeloid growth by the same biomechanical mechanism, then activating RAS mutations will be restricted to children with malignant myeloid disorders who do not have NF-1. We studied 71 children, including 28 with bone marrow monosomy 7 syndrome (Mo7), 35with juvenile chronic myelogenous leukemia (JCML), three with other forms of preleukemia, and five with acute myelogenous leukemia (AML), for activating mutations of KRAS and NRAS. The incidence of RAS mutations was 21% (12 of 55) in patients without NF-1 and 0% (zero of 16) in children with NF-1 (P = .04). Among the 55 patients who did not have NF-1, we found RAS mutations in four of 27 with Mo 7, in five of 24 with JCML, in two of 3 with AML, and in a patient with myeloproliferative syndrome (MPS). These data from primary human cancer cells provide strong genetic evidence that NF1 limits the growth of myeloid cells by regulating Ras.
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PMID:Genetic analysis is consistent with the hypothesis that NF1 limits myeloid cell growth through p21ras. 794 98


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