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Results for “MYC amplification”

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PubMed1989

N-myc amplification and neuron-specific enolase production of a neuroblastoma cell line and germ cell tumor cell lines.

N-myc gene amplification of the gynecological malignant tumor cell lines and a neuroblastoma cell line was studied by the Southern hybridization method along with the production of neuron-specific enolase (NSE) by these cell lines. N-myc amplification and NSE production were observed side by side in three cell lines: neuroblastoma cell line HSNB, endodermal sinus tumor cell line HAEST, and malignant teratoma cell line HUOT. However, N-myc amplification and NSE production disappeared gradually following successive passages of the HAEST and HUOT lines. With respect to the HUOT line, these parameters disappeared along with the cells of nervous origin. N-myc amplification and NSE production were not observed in nine other cell lines.

Female↗

PubMed2003

Multiple effects of paclitaxel are modulated by a high c-myc amplification level.

Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm.

Antineoplastic Agents, Phytogenic↗

PubMed2000

C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance.

Data from basic research suggests that amplification of the proto-oncogene c-myc is important in breast cancer pathogenesis, but its frequency of amplification and prognostic relevance in human studies have been inconsistent. In an effort to clarify the clinical significance of c-myc amplification in breast cancer, we conducted a comprehensive literature search and a meta-analysis in which 29 studies were evaluated. The weighted average frequency of c-myc amplification in breast tumours was 15.7% (95% CI = 12.5-18.8%), although estimates in individual studies exhibited significant heterogeneity, P<0.0001. C-myc amplification exhibited significant but weak associations with tumour grade (RR = 1.61), lymph-node metastasis (RR = 1.24), negative progesterone receptor status (RR = 1.27), and postmenopausal status (RR = 0.82). Amplification was significantly associated with risk of relapse and death, with pooled estimates RR = 2.05 (95% CI = 1.51-2.78) and RR = 1.74 (95% CI = 1.27-2.39), respectively. This effect did not appear to be merely a surrogate for other prognostic factors. These results suggest that c-myc amplification is relatively common in breast cancer and may provide independent prognostic information. More rigorous studies with consistent methodology are required to validate this association, and to investigate its potential as a molecular predictor of specific therapy response.

Breast Neoplasms↗

PubMed1997

Clinical relevance of TRKA expression on neuroblastoma: comparison with N-MYC amplification and CD44 expression.

TRKA expression was evaluated on 122 untreated neuroblastomas by immunohistochemistry using an antibody with predetermined specificity. This procedure is simple and reliable for protein detection at cellular level in a routine clinical setting. Fourteen tumours were classified as benign ganglioneuroma with a restricted expression of TRKA on ganglion cells; these patients were excluded from the following analysis. A total of 108 tumours were classified as neuroblastoma or ganglioneuroblastoma; 74 expressed TRKA protein, which strongly correlated with low stage, absence of N-MYC amplification, age (<1 year), CD44 expression and favourable clinical outcome. In a univariate analysis including tumour stage, age, histology, N-MYC amplification, CD44 and TRKA expression, all parameters had significant prognostic value. The absence of TRKA expression on CD44-positive or N-MYC non-amplified tumours permits the characterization of a subgroup of patients with intermediate prognosis. However, in a multivariate analysis taking into consideration the prognostic factors mentioned above, CD44 and tumour stage were the only independent prognostic factors for the prediction of patients' event-free survival.

Analysis of Variance↗

PubMed1989

N-myc amplification and neuronal differentiation in human primitive neuroectodermal tumors of the central nervous system.

Despite the phenotypic similarities between primitive neuroectodermal tumors of the central nervous system, childhood neuroblastoma, and peripheral neuroepithelioma, a histogenetic relationship among these neoplasms has not been shown. High levels of N-myc expression occur selectively in developing brain and in some embryonic tumors of neural origin. N-myc amplification and high levels of N-myc expression in childhood neuroblastoma have been correlated with disease stage and prognosis. To determine whether the copy number of the N-myc gene in primitive neuroectodermal tumors of the central nervous system is altered, we examined 20 primitive neuroectodermal tumors by Southern and/or slot blot hybridization to a 1-kilobase N-myc genomic DNA sequence and a 492-base pair N-myc-specific subclone as well as to a 1.1-kilobase albumin complementary DNA sequence as a control for gene copy number. Amplification of the N-myc gene was detected in two cerebellar tumors both of which exhibited neuronal differentiation by light microscopy. These tumors had not been treated previously. Of the remaining 18 tumors, eight were undifferentiated, three showed early neuroblastic, and seven focal glial differentiation. These findings suggest a possible relationship between N-myc amplification and neuronal differentiation.

Brain Neoplasms↗

PubMedDate not supplied

Aneuploidy of chromosome 8 and C-MYC amplification in individuals from northern Brazil with gastric adenocarcinoma.

BACKGROUND: Gastric cancer is the third most frequent type of neoplasia. In northern Brazil, the State of Pará has a high incidence of this type of neoplasia. Limited data are available so far on the genetic events involved in this disease. MATERIALS AND METHODS: Dual-color fluorescence in situ hybridization (FISH) for the C-MYC gene and chromosome 8 centromere was performed in 11 gastric adenocarcinomas. RESULTS: All cases showed aneuploidy of chromosome 8 and C-MYC amplification, in both the diffuse and the intestinal histopathological types of Laurén. No correlation was found between polysomy 8 and the histopathological characteristics of the tumors. C-MYC amplification, like homogeneously-stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Translocation of C-MYC was observed only in the diffuse-type. CONCLUSION: Chromosome 8 can be used as a marker in the diagnosis of gastric adenocarcinoma. The C-MYC oncogene requires further studies in order to verify if it is, when amplified, an etiological cause of transformation or a consequence of the proliferation process.

Adenocarcinoma↗

PubMedDate not supplied

Trisomy 4 associated with double minute chromosomes and MYC amplification in acute myeloblastic leukemia.

A case of de novo acute myeloblastic leukemia (AML) M2, with trisomy 4 and double minute (dmin) chromosomes is reported. Amplification of the MYC gene ascertained by FISH was associated with dmin. A review of the literature of trisomy 4-dmin-associated AML shows that this entity preferentially occurs in elderly women and is not always associated with previously identified exposition to mutagens.

Age Factors↗

PubMed2002

Loss of expression of death-inducing signaling complex (DISC) components in lung cancer cell lines and the influence of MYC amplification.

We have previously reported that the key apoptosis related gene caspase 8 (CASP8) is frequently silenced in small cell lung cancer (SCLC) tumors and cell lines usually, but not always, by aberrant promoter methylation. Because CASP8 is a key component of the death-inducing signaling complex (DISC) when specific death receptors (including DR4, DR5, FAS) are activated by their specific ligands (TRAIL/FASL), we examined expression of the components of the DISC complex in lung cancer cell lines. MYC family members are frequently amplified (MYC+ve) in SCLC, and MYC is a potent inducer of apoptosis. We examined 34 SCLC lines (12 of which were MYC+ve) and 22 NSCLC lines. CASP8 gene expression was frequently lost (79%) at message and protein levels in SCLC but not in non-SCLC (NSCLC). MYC amplification was present in 45% of SCLC cell lines, which had lost CASP8 expression, but not in any of the CASP8 positive lines. The frequency of CASP8 loss was significantly higher in MYC+ve SCLC compared to MYC-ve SCLC or in NSCLC. Analyses of other DISC components showed significantly higher rates of loss of expression of CASP10, DR5, FAS and FASL in SCLC compared to NSCLC. The loss of expression of proapoptotic DISC components was significantly higher in MYC+ve SCLC cell lines and these lines were completely resistant to TRAIL. Expression of CASP10 (a caspase closely related to CASP8) was frequently absent at the protein level in both SCLC and NSCLC lines. Expression of c-FLIP (proteolytically inactive homolog of CASP8) was inversely related to expression of CASP8. Our major conclusions are: (a) The death receptor pathway is differently inactivated at multiple levels in lung cancer cell lines; and (b) MYC amplification in SCLC is associated with inactivation of most components of the DISC complex, with resistance to TRAIL and with expression of c-FLIP. These findings may have considerable clinical and therapeutic implications.

Carcinoma, Non-Small-Cell Lung↗

PubMed1995

Prognostic value of erb-B2 and myc amplification in breast cancer imprints.

BACKGROUND: Amplification of erb-B2 and myc shows prognostic value in patients with operable breast cancer. Amplification is usually detected in tumor samples remaining after pathologic work-up, preventing the examination of small tumors. METHODS: Tumor imprints that contained low numbers of contaminating normal cells were obtained from small tumors. The prognostic value of erb-B2 and myc amplification in imprint breast preparations was examined, using the polymerase chain reaction (PCR) to determine gene copy number. Tumor material was obtained from 162 patients with breast cancer operated 1975-1976. RESULTS: Amplification of erb-B2 existed in 21% and myc in 16% of the patients. Both erb-B2 and myc amplification showed prognostic significance in univariate analysis for survival and relapse free survival. In multivariate analysis, erb-B2 was a significant factor. In small tumors less than 13 mm in greatest dimension, erb-B2 showed prognostic significance for survival but not for relapse free survival. CONCLUSIONS: The use of imprints/PCR allows the detection of gene amplification in breast cancer. The procedure is suitable for the analysis of small tumors and can be used to examine very small tumors, such as those detected mammographically.

Analysis of Variance↗

PubMed2006

Interrelationship between chromosome 8 aneuploidy, C-MYC amplification and increased expression in individuals from northern Brazil with gastric adenocarcinoma.

AIM: To investigate chromosome 8 numerical aberrations, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histopathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immunostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneuploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level of chromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal-type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic pathways.

Adenocarcinoma↗

PubMed2006

Non-Hodgkin's lymphomas with Burkitt-like cells are associated with c-Myc amplification and poor prognosis.

Out of 344 patients with newly diagnosed non-Hodgkin's lymphoma (NHL), this study identified 16 patients presenting Burkitt-like cells (BLCs) after cytological and/or histological review. Conventional cytogenetic analysis showed at diagnosis complex chromosomal abnormalities in 13 cases and a normal karyotype in three cases. However, neither t(8;14)(q24;q32) nor the variants t(2;8)(p12;q24) or t(8;22)(q24;q11) was detected. FISH studies showed c-MYC amplification in all cases with four to more than seven copies in 10 - 77% metaphase or inter-phase cells. This study did not observe any gene fusion signal for c-MYC/IgH excluding a t(8;14) translocation and partial tri or polysomy of chromosome 8. It also excluded in that cases a break apart for the c-MYC locus. This study also never detected IgL/c-MYC, IgK/c-MYC or X-c-MYC. The BLCs were present whatever the lymphoma sub-type: follicular lymphoma (FL) was diagnosed in six out of 16 patients, mantle cell lymphoma (MCL) in four out of 16 patients, marginal zone lymphoma (MZL) in two out of 16 patients and diffuse large B-cell lymphomas (DLBCL) in three out of 16 patients. One additional patient presented a T-cell lymphoma. The clinical course was aggressive with a poor prognosis, as death occurred in nine patients, within 6 months after diagnosis for eight of them. These data could suggest a sub-group of NHL patients (15 B-NHL, 1 T-NHL) have been identified with a poor prognosis characterized by the association of Burkitt-like cells and c-MYC amplification without t(8;14)(q24;q32) or its variants. The possibility that this profile may represent a distinct morphologic NHL sub-set remains to be determined on a large cohort of patients.

Adult↗

PubMed1990

[Relationship between human papillomavirus and oncogenes (c-myc, N-myc) amplification in human cervical cancers].

The human papillomavirus detection and oncogenes amplifications were studied on DNAs from fifteen cervical cancers. We detected HPV16 and HPV18 using Southern blot hybridization and polymerase chain reaction (PCR) technique. The positive subjects of HPVs were eight cases (53%) observed by Southern blot hybridization and fourteen cases (93%) by PCR technique. The gene amplifications of oncogenes (c-myc and N-myc) were analysed by slot-blot method and were observed in c-myc but not in N-myc. The "LARGE" gene amplification (more than five fold) in c-myc was observed in one case (7%) and the "SMALL" gene amplifications (less than five fold) were observed in six cases (40%) in human cervical cancers. Although one of five cases (20%) with HPV16 was present c-myc gene amplification, all of three cases (100%) with HPV18 were found c-myc gene amplifications. In two out of three cases obtained more than three fold c-myc gene amplifications, HPV were not detectable. It is suggested that the negative correlation between gene amplification and numbers of HPV copies exist in advanced cervical cancers.

Adult↗

PubMed1984

A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer.

Amplifications of two oncogenes, c-K-ras-2 and c-myc, were found in a human lung giant cell carcinoma (LGCC) Lu-65, which is maintained in nude mice. The extent of c-K-ras-2 and myc amplifications were estimated to be 10- and 8-fold, respectively, by means of the Southern hybridization procedure. In addition, NIH3T3 cells were transformed by transfection of Lu-65 DNA and the transforming gene was identified as c-K-ras-2. c-K-ras-2 genes were cloned from a gene library of Lu-65 and a single point mutation causing a substitution of cysteine for glycine in codon 12 was found by DNA sequencing. It was concluded that the amplification of the c-myc and c-K-ras-2 genes are accompanied by point mutational activation of c-K-ras-2 in the human LGCC Lu-65. This is the first report of multiple gene amplification accompanied by a point mutation of oncogenes in human cancer cells, providing further support for the idea that co-operation of at least two activated cellular oncogenes is required for carcinogenesis.

Amino Acid Sequence↗

PubMed2006

c-myc amplification is frequent in esophageal adenocarcinoma and correlated with the upregulation of VEGF-A expression.

BACKGROUND: Deregulation of c-myc plays a major role in the carcinogenesis of human malignancies. We investigated the amplification of the c-myc gene in a surgical series of Barrett cancers. METHODS: Primary resected esophageal (Barrett) adenocarcinomas (n = 84) were investigated for c-myc amplification using chromogene in situ hybridization. Tumor samples were assembled in a tissue microarray. c-myc gene dosage was correlated with clinicopathologic parameters, including the survival and gene expression of cyclooxygenases (COX-1 and COX-2) and proangiogenic growth factors (VEGF-A and VEGF-C). RESULTS: The majority (70 of 84; 83.3%) exhibited amplification of the c-myc gene. There were low-level amplifications in 63 (75.0%) cases and high-level amplifications in 7 (8.3%) cases. No amplification was found in 14 (16.7%) cases. Tumors without c-myc amplification had lower VEGF-A, VEGF-C, and COX-2 expression levels than tumors with low-level and high-level c-myc amplification (statistically significant for VEGF-A; P = .0348). c-myc amplification was not correlated with clinicopathological parameters or survival. Only diffuse and mixed-type tumors, according to Lauren classification, exhibited c-myc amplifications more frequently (P = .0466). CONCLUSIONS: Amplifications of the c-myc gene are frequent in Barrett cancer. c-myc may be involved in the regulation of angiogenesis.

Adenocarcinoma↗

PubMed2006

Fluorescence in situ hybridization analysis of c-myc amplification in stage TNM prostate cancer in Japanese patients.

OBJECTIVE: Genetic aberration such as the amplification of c-myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c-myc gene), related to the progression and survival in advanced (Stage C) prostate cancer. MATERIALS AND METHODS: We used dual-probe fluorescence in situ hybridization with a centromere-specific probe for chromosome 8 (8cen), and with a region-specific probe for c-myc (8q24) to evaluate genetic changes in tumor samples from 50 patients who had undergone radical retropubic prostatectomy from 1986 to 2001. RESULTS: We classified the 8cen and c-myc copy numbers as normal, gain and amplification. The carcinoma foci with extra copies of c-myc, which was defined in 35 cases (70%), were divided into two groups: (a) a simple gain of the whole chromosome 8 (no increase in the c-myc copy number relative to the chromosome 8 centromere), which was identified in 15 cases (30%); and (b) a substantial amplification of c-myc (additional increases [AI] in the c-myc copy number relative to the chromosome 8 centromere), which was detected in 20 cases (40%). AI-c-myc was strongly associated with higher histopathological grades and Gleason's scores (P = 0.0330, 0.0190, respectively). Patients with the AI-c-myc had earlier disease progression (P = 0.0029) and earlier cancer death (P = 0.0087) than did patients with normal patterns. CONCLUSION: Identification of an AI-c-myc may serve as a potential marker of prostate cancer progression.

Aged↗

PubMedDate not supplied

C-myc amplification and cluster analysis in human gastric carcinoma.

The tumour samples ot 23 patients (9 male, 14 female, aged 28-85) were randomly selected for the study. DNA was isolated from paraffin embedded tissue for quantitative dot-blot hybridization, in order to determine the amplification values for the c-myc and K-ras oncogenes. The clinical and histological parameters studied were as follows: grade, TNM staging system, Lauren's histological type, localization and the severity of the disease. Amplified c-myc was found in 6 cases. Amplification was concomitant with c-myc overexpression detected with immunohistochemical staining. The amplification--9.1-fold on the average (ranging from 2.12 to 18.2) was significantly associated with the presence of distant metastasis (corr. coeff.: 0.5623, p < 0.01), but with none of the other parameters. No case with K-ras amplification was recorded. The result of the multivariate cluster analysis proved that age was the decisive factor in the segregation process. This age-related distribution (69 vs. 40, p < 0.001), however, did not coincide with either the incidence of distant metastasis or c-myc amplification.

Adenocarcinoma↗

PubMed1997

Is the presence of distant metastasis associated with c-myc amplification in gastric cancer?

The expression of the c-myc oncogenes has already been reported in human gastric carcinoma. Overexpression can be the consequence of oncogene amplification and often correlates with different prognostic factors. Authors investigated the value of c-myc oncogene amplification in 23 patients (9 male, 14 female, aged 28-85 yrs) with gastric cancer and its correlation to the following clinical and histopathological parameters: grade, TNM stage, Lauren's type, localisation and severity of disease. DNA was isolated from formalin-fixed, paraffin embedded tissue for quantitative dot-blot hybridisation. Amplified c-myc was found in 6 out of 23 cases. Its values ranged from 2.12 up to 18.2 (average 9.1). Significant association was found between the presence of c-myc amplification and distant metastasis (corr. coeff.: 0.5623, p < 0.01). High scores of the other parameters also correlated with c-myc, albeit not significantly. The result of cluster analysis, based on the similarity of the parameter values for the individual patients proved that the age was the decisive factor in creating two groups. The distribution of patients into these groups did not seem to coincide with the presence of c-myc amplification or distant metastasis, inspite of the proved correlation between them.

Adult↗

PubMed1994

Loss of the putative tumor suppressor-gene locus 1p36 as investigated by a PCR-assay and N-myc amplification in 48 neuroblastomas: results of the German Neuroblastoma Study Group.

48 primary neuroblastomas have been examined for an amplified N-myc and loss of the putative tumor suppressor-gene locus 1p36 by loss of heterozygosity studies (LOH 1p36). In 25% of these tumors N-myc amplification and/or a LOH 1p36 was detected, and these patients had a bad prognostic clinical outcome. 75% of the tumors neither had an amplified N-myc nor a LOH 1p36, and these patients had a much better prognosis. Thus, tumor genetic changes can subdivide two types of neuroblastoma with profound different clinical behavior. Detection of these genetic changes at diagnosis could help in front-line risk adapted therapy stratifications in neuroblastoma.

Base Sequence↗