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Results for “MYC amplification”

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PubMed1989

Amplification of both c-myc and c-raf-1 oncogenes in a human osteosarcoma.

Fourteen human bone and soft part tumor tissues were screened by Southern blot hybridization using five oncogene probes (c-myc, c-K-ras, c-fos, c-raf-1, and N-myc). Amplification of c-myc was found in two osteosarcomas and one malignant fibrous histiocytoma. One of these osteosarcomas had amplified c-raf-1 gene. Rearrangement of the amplified gene was not observed. This is the first report of c-raf-1 amplification in human cancer tissues.

Adolescent↗

PubMed1992

Prognostic value of N-myc oncogene amplification and S-100 protein positivity in children with neuroblastic tumors.

Data on 43 neuroblastic tumors (30 neuroblastomas and 13 ganglioneuroblastomas) obtained from 22 untreated and 21 pretreated children, were analyzed to determine the correlation between N-myc oncogene amplification and immunohistochemically identified S-100 protein positivity. Sixteen patients in whom the tumor showed significant amplification of N-myc (more than ten copies) died, irrespective of S-100 protein positivity and other conventional factors. Among 27 patients with low amplification of N-myc (less than ten copies), the estimated progression-free survival for those whose tumors had numerous S-100 protein-positive cells (P group), and few or no positive cells (N group) was 75% and 17%, respectively (p < 0.0001). Thus, in addition to N-myc oncogene amplification as a reliable indicator of outcome, S-100 protein positivity should be useful for prediction of prognosis in children with neuroblastic tumors showing low amplification of N-myc. Correlations among these results and other clinical factors are briefly discussed.

Adrenal Gland Neoplasms↗

PubMed1993

Detection of N-myc gene amplification by fluorescence in situ hybridization. Diagnostic utility for neuroblastoma.

We assessed fluorescence in situ hybridization (FISH) as an alternative to Southern blot analysis for determination of N-myc gene amplification in neuroblastoma. In the 44 pediatric solid tumor cell lines examined (20 neuroblastomas), the mean number of N-myc copies determined by FISH correlated closely with Southern blot results. There was wide intercellular variability in gene copy number in tumors that had evidence of amplification; however, tumors judged to be non-amplified completely lacked any cells with high N-myc copy number. FISH provided reliable estimates of N-myc amplification in 12 clinical samples even when the percentage of tumor was low. The other advantages of FISH over Southern blot analysis were speed and technical simplicity, ability to discern heterogeneous gene amplification among tumor cells in the same specimen, and capacity to determine the source of the amplified N-myc signal, whether extrachromosomal double-minute chromosomes, expanded intrachromosomal regions, or chromosome 2 aneuploidy. We conclude that FISH would refine the analysis of N-myc amplification in neuroblastoma and thus improve the assignment of patients to prognostic groups based on this unfavorable risk factor.

Blotting, Southern↗

PubMed2003

Investigation of c-myc and p53 gene alterations in the tumor and surgical borderline tissues of NSCLC and effects on clinicopathologic behavior: by the FISH technique.

Genetic alterations on the primary tumoral tissues and surgical borderline tissues of 51 patients with NSCLC on which radiotherapy and chemotherapy had not been performed were analyzed by using the FISH method with locus-specific probes for p53 tumor suppressor gene and c-myc oncogene and centromere-specific probes for chromosome 17 and chromosome 8 on which these genes are located. P53 deletions were detected in 7 patients (13.7%), c-myc amplification in 4 patients (7.8%), monosomy 17 in 2 patients (3.9%) and trisomy 8 in 3 patients (5.8%), and a high level of polyploidy in tumoral tissues of 6 patients (11.7%). P53 deletion and c-myc amplification were found at surgical borderlines of 2 patients and 1 patient, respectively. Although both p53 deletion and c-myc amplification have low frequency at surgical border tissues, not only their detection is important for the follow-up of recurrency and metastasis, but it is also important for genetical and pathological staging. The results of this study show that c-myc amplification in NSCLC is related to the shortening of survival (p < 0.01). C-myc amplification and p53 deletion are also effective for the occurrence of metastasis (p < 0.05) and the effect of c-myc amplification in this matter is much higher than p53 deletion. The gain or loss of copy number of chromosome 8 and monosomy 17 show parallel effects with c-myc amplification and p53 deletion, respectively, on the clinicopathological behavior of tumors.

Adult↗

PubMed1998

Detection of MYC gene amplification in malignant lymphomas.

The role of oncogene or tumor supressor gene in Epstein-Barr virus (EBV) associated malignant lymphomas (MLs) is poorly understood. We examined 36 MLs (21 EBV positive and 15 EBV negative) and 6 reactive hyperplasias for the presence of myc gene amplification. Polymerase chain reaction (PCR) technology was used to examine the state of amplification of the proto-oncogene c-myc in formalin-fixed paraffin-embedded tissues. Variable degrees of myc gene amplification were detected in reactive hyperplasias and MLs. However, significant increase of c-myc copy numbers above 3 times were only found in 12 out of 31 non-Hodgkin's MLs (38.7%), in which 6 cases were EBV positive and 6 cases were EBV negative. In conclusion, myc gene amplification appears to play a part in MLs but no correlation was found between EBV infection and myc gene amplification.

Castleman Disease↗

PubMed2003

[Detection of n-myc gene amplification in neuroblastoma using polymerase chain reaction based methods].

We have used semiquantitative and real-time quantitative PCRs to detect n-myc gene-amplification in 21 frozen neuroblastoma biopsies and IMR 32 cell line in order to predict biological behaviour of the tumors. Two primer pairs were used in the semiquantitative method to co-amplify a 520-bp fragment of the beta -globin gene -used as a single copy reference standard -and a 258-bp fragment of the n-myc gene. After 30 cycles the PCR products were electrophoresed through an agarose gel and were compared to each other with use of a gel-densitometer. Real-time quantitative analysis was performed in a LightCycler instrument. A single primer pair was used to amplify a 120-bp fragment of the n-myc oncogene and a LC640-labelled fluorescent probe pair to detect the product. Calibration curve, which was set up from a serial dilution including samples with 1, 2, 10, 13, 25-fold n-myc oncogene amplification, was employed for quantitative analysis. Semiquantitative method did not show distinct difference between tumor groups with no amplification and less than 10-fold amplification, while quantitative LightCycler analysis was able to detect even 2-fold amplification. In situ PCRs were performed in two cases of differentiated tumor samples which contained n-myc amplification. We used biotinylated ATP labelling and the same primer pair as for the LightCycler analysis.In both cases differentiated cell forms did not show n-myc gene amplification, while considerable amplification was detected in the neuroblasts.

DNA Probes↗

PubMed1992

N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis.

N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow-up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma.

Biopsy, Needle↗

PubMed1998

N-myc gene amplification in rhabdomyosarcoma detected by fluorescence in situ hybridization: its correlation with histologic features.

Fluorescence in situ hybridization (FISH) was applied to 15 alveolar rhabdomyosarcomas (A-RMSs) and 14 embryonal RMSs (E-RMSs) to detect N-myc (also called MYCN) oncogene amplification. The results were compared with histologic characteristics and clinical factors. The number of surviving patients in each subtype was 5 of 15 with A-RMS and 5 of 14 with E-RMS. N-myc amplification was detected in 9 of the 15 A-RMSs but in none of the 14 E-RMSs. Tumor cells exhibiting N-myc amplification were identified only in the alveolar area in two A-RMSs, and they demonstrated a histologic mixture of alveolar and embryonal patterns. The remaining seven cases with an amplified N-myc showed a conventional alveolar pattern. Among the 15 A-RMSs, the survival rate of patients with tumors showing nonamplified N-myc and amplified N-myc oncogene was 4 (66%) of 6 and 1(11%) of 9, respectively (P < .05). No significant difference was observed between the other clinical findings (age, primary sites, clinical stages) of the N-myc-amplified and nonamplified tumors. Therefore, we concluded that the N-myc gene amplification, which is characteristic of a particular subtype of A-RMS, might be useful as a prognostic factor for an unfavorable outcome.

Adolescent↗

PubMed2006

Marked and independent prognostic significance of the CpG island methylator phenotype in neuroblastomas.

The CpG island methylator phenotype (CIMP) was closely associated with poor overall survival (OS) in Japanese neuroblastoma (NBL) cases in our previous study. Here, in German NBL cases, CIMP(+) cases (n=95) showed markedly poorer OS (hazard ratio (HR)=9.5; P<0.0001) and disease-free survival (DFS) (HR=5.4; P<0.0001) than CIMP(-) cases (n=50). All the 23 cases with N-myc amplification had CIMP. Among the remaining cases without N-myc amplification, CIMP(+) cases (n=27) had a poorer OS (HR=4.5; P=0.02) and DFS (HR=5.2; P<0.0001) than CIMP(-) cases (n=95). In multivariate analysis, CIMP and N-myc amplification had an influence on OS and DFS independent of age and disease stage. CIMP had a stronger influence on DFS than N-myc amplification while N-myc had a stronger influence on OS.

Adolescent↗

PubMed1990

N-myc gene amplification and other prognosis-associated factors in neuroblastoma.

The correlation between N-myc gene amplification and heretofore known prognosis-associated factors was studied in 23 cases of neuroblastoma, comprising a total of 29 tumors (23 primary and six metastatic), examined in and after 1983. DNAs were extracted from tumor tissues preserved at -70 degrees C and digested with the restriction enzyme EcoRI. Southern blotting analysis was performed on these DNAs with the N-myc probe labelled with alpha-32P-dCTP. Prognosis-associated factors studied were age at diagnosis, stage, primary site, histological type, blood biochemistry tests, and catecholamine metabolites in urine. Amplification of N-myc gene was observed only in the cases in which primary site was the adrenal gland, but the relation to the stage, histological type, and prognosis was not as apparent as reported by other investigators. However, the amounts of catecholamine metabolites were low in the cases with amplification, and this suggests immaturity of catecholamine metabolism in the tumor with N-myc gene amplification.

Blotting, Southern↗

PubMed1991

Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study.

We assessed tumor cell DNA content (ploidy) and N-myc gene copy number as predictors of long-term disease-free survival in 298 children with neuroblastoma. Diploid tumor stem lines were identified in 101 patients (34%), clonal hyperdiploid abnormalities in 194 (65%), and hypodiploid stem lines in three (1%). In children with widely disseminated tumors at diagnosis (stage D), ploidy had a highly age-dependent influence on prognosis. Among infants (less than 12 months) treated with cyclophosphamide-doxorubicin, hyperdiploidy was closely associated with long-term disease-free survival (greater than 90% of cases), while diploidy invariably predicted early treatment failure (P less than .001). Similarly, in children 12 to 24 months of age who were treated with cisplatin-teniposide and cyclophosphamide-doxorubicin, diploidy uniformly predicted early failure, whereas half of the children with hyperdiploidy achieved long-term disease-free survival (P less than .001). There was no relationship between ploidy and treatment outcome in children older than 24 months with stage D tumors who had a very low probability of long-term disease-free survival (less than 10%). N-myc gene amplification was detected in 37 (25%) of the 147 tumors tested, with the remainder showing single-copy levels of the gene. N-myc gene amplification was more frequent in diploid than in hyperdiploid tumors (23 of 57 v 14 of 87, P = .001) and predicted a high likelihood of early treatment failure. In children younger than 2 years with disseminated neuroblastoma, tumor cell ploidy and N-myc gene copy number provide complementary prognostic information that will distinguish patients who can be cured on current regimens from those who require new treatment strategies.

Age Factors↗

PubMed2001

Analysis of c-myc DNA amplification in non-small cell lung carcinoma in comparison with small cell lung carcinoma using polymerase chain reaction.

Previous studies of c-mvc DNA amplification in lung cancer have focused primarily on analysis of small cell carcinoma or its tumor cell lines. There are few data about c-myc DNA amplification in histological types of lung cancer other than small cell carcinoma. Therefore the present study was conducted to investigate c-myc oncogene amplification in non-small cell lung carcinoma. We studied 46 lung tumor specimens for c-myc DNA amplification (15 adenocarcinomas, 15 squamous cell carcinomas, 6 large cell carcinomas, and 10 small cell carcinomas). Polymerase chain reaction, digoxigenin DNA labeling, and electrophoresis were utilized to investigate the c-myc copy number in the lung tumor specimens. The c-myc copy number of non-small cell carcinoma ranged from 1.5 to more than 20.0 in adenocarcinoma and squamous cell carcinoma, and from 6.0 to 12.0 in large cell carcinoma. That of small cell carcinoma ranged from 1.8 to 12.0. The c-myc copy number of non-small cell carcinoma was significantly higher than that of small cell carcinoma (Wilcoxon rank sum test, Z=2.06 P=0.040). However, the differences in c-myc copy number among these four histological types were not statistically significant. Amplification of c-myc (more than 4 copies) was observed not only in small cell carcinoma but also in nonsmall cell carcinoma at similarly high frequency (12/15 in adenocarcinoma and squamous cell carcinoma, 6/6 in large cell carcinoma, and 9/10 in small cell carcinoma).

Adenocarcinoma↗

PubMed1991

N-myc gene amplification and neuron specific enolase production in immature teratomas.

The primary tumour tissues from 13 teratomas were investigated, 3 cases of immature teratoma (1 of pure type and 2 of mixed type), 5 cases of dermoid cyst, and 5 cases of mature solid teratoma, with special reference to N-myc gene amplification, productivity of neuron specific enolase (NSE), and the presence of double minutes (DMs). The possible relationship between these variables and malignancy of the tumours was also examined. N-myc gene amplification and NSE production were recognized in the primary tumour tissues and the first and the third passage cultured cells of all of the 3 cases of immature teratoma containing immature neural tissues. In 2 cases DMs were recognized. In dermoid cysts and mature teratoma, neither N-myc gene amplification nor NSE production were recognized in either the primary tumour tissues or cultured cells. The chromosomes were normal. Malignancy of teratoma is generally decided by the clinical stage and histological grade, but a more securely based decision is necessary where an immature teratoma contains immature neural tissues. The presence of N-myc gene amplification, NSE productivity and the presence of DMs may be valuable.

Adult↗

PubMed1995

Lack of correlation of N-myc gene amplification with prognosis in localized neuroblastoma: a Pediatric Oncology Group study.

Multiple copies of N-myc proto-oncogene are only rarely detected in localized neuroblastomas (NBs), and the prognostic relevance of amplification in this subset of patients is not clear. We analyzed a series of 850 children with NB admitted to a Pediatric Oncology Group NB Biology Study and identified six patients with localized NBs harboring N-myc gene amplification. Three patients whose tumors showed favorable histology by Shimada classification and low-risk histological features according to the Joshi classification have remained disease-free, whereas two of three patients with unfavorable histology tumors have developed recurrent disease. Although earlier studies have indicated that N-myc amplification is associated with diploid DNA content, flow cytometric analysis revealed that only two of the localized tumors contained stem lines with diploid DNA content. Loss of chromosome 1p was not detected by fluorescence in situ hybridization in the two tumors examined. N-myc protein was detected by immunohistochemical studies in four of the five NBs analyzed. However, N-myc protein was not visualized in one of the tumors with stroma-rich histology, and Western blot analysis revealed only low levels of N-myc protein expression in another NB with favorable histology. These studies indicate that the presence of N-myc amplification in localized NBs does not necessarily portend an adverse outcome. Furthermore, the biological features of this subset of N-myc-amplified NBs appear to differ from those of more advanced N-myc-amplified tumors.

Child↗

PubMed1988

Cytogenetic abnormalities in human small cell lung carcinoma: cell lines characterized for myc gene amplification.

Nine cell lines established from various malignant tissues of patients with small cell lung carcinoma (SCLC) were examined for chromosomal abnormalities and myc gene amplification. Cytogenetic studies revealed that all cell lines were aneuploid, often with a bimodal distribution with modal concentrations in the hypodiploid and hypertriploid range. With respect to chromosome #3, deletions of 3p were confined to six of nine SCLC "classic" lines. The region of overlap of the observed 3p deletions lies within 3p21-3p24 which is in agreement with previous assignments. Six of the nine lines tested with c-, N-, and L-myc probes showed an increase of between ten- and 100 fold in myc gene copy number. Coamplification of two or more of these genes was not observed in any cell line. Five of the six lines with myc gene amplification had cytogenetic markers of gene amplification either in the form of homogeneously staining regions (HSR) or double minutes (DM). Our results confirm that cytogenetically visible deletions of 3p are often present in cell lines established from patients with SCLC, and that mutually exclusive c-, L-, or N-myc gene amplification is also a common event in SCLC cell lines.

Carcinoma, Small Cell↗

PubMed1987

Neoplastic transformation by the human gene N-myc.

Amplification and abundant expression of a gene known as N-myc are found frequently in advanced stages of human neuroblastoma and may play a role in the genesis of several malignant human tumors. Previous studies have shown that N-myc can cooperate with a mutant allele of the proto-oncogene c-Ha-ras to transform embryonic rat cells in culture. Here we show that N-myc can also act alone to elicit neoplastic growth of an established line of rat fibroblasts (Rat-1). We used recombinant DNA vectors to express either N-myc or its kindred gene c-myc in transfected cells. Both genes caused morphological transformation, anchorage-independent growth, and tumorigenicity. We noticed two variables that appeared to influence the ability to isolate cells transformed by N-myc and c-myc: the abundance in which the genes were expressed and biological selection to eliminate untransformed cells from the cultures. Our findings sustain the belief that N-myc is an authentic proto-oncogene, lend further credibility to the role of N-myc in the genesis of human tumors, and establish a convenient assay that can be used to explore further the properties of both N-myc and c-myc.

Animals↗

PubMed1994

Expression of neuronal src mRNA as a favorable marker and inverse correlation to N-myc gene amplification in human neuroblastomas.

Neuron-specific src mRNA, which is expressed in human brain tissue by alternative splicing, is associated with neural differentiation. Neuronal c-srcNI expression may be associated with the ability of neuroblastomas to mature; furthermore, c-srcN2 mRNA is induced in chemically differentiated neuroblastoma cells in vitro. The prognosis of a patient with a neuroblastoma is strongly affected by the ability of the tumor to differentiate in vivo. In order to clarify the relationship between neuronal src mRNA expression and the clinical outcome of a neuroblastoma, we analyzed the expression of src mRNA in neuroblastoma tissues from 28 patients by SI-nuclease-protection assay. N-myc gene amplification was also examined by Southern blot hybridization. The clinical significance of neuronal src mRNA expression and its relevance to N-myc gene amplification was also investigated. A high ratio (more than 10%) of c-srcN2 mRNA expression was observed in all early-stage tumors and in advanced neuroblastomas with a favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive clinical phenotype, c-srcN2 mRNA expression was found at a low ratio (below 10%). Genomic amplification of the N-myc gene and expression of c-srcN2 mRNAs were inversely correlated. When combined with other prognostic markers such as N-myc gene amplification, the expression of c-srcN2 mRNA may be a new biological marker to predict the prognosis of patients with neuroblastomas.

Blotting, Southern↗

PubMed1998

Nonsyntenic amplification of MYC with CDK4 and MDM2 in a malignant mixed tumor of salivary gland.

Karyotypic analysis of a metastatic malignant mixed tumor of the salivary gland revealed the presence of double minute chromosomes (dmin), indicative of gene amplification. Comparative genomic hybridization analysis of DNA extracted from the primary and a renal metastasis indicated overt amplification of DNA sequences derived from 8q23-24 and 12q13-15 regions. Subsequent Southern blot analysis of tumor DNA from the metastasis with the use of probes previously mapped to those regions indicated amplification of MYC at 8q23-24 and CDK4 and MDM2 at 12q13-15. Fluorescence in situ hybridization of differentially labeled MYC and MDM2 genes hybridized to tumor metaphase chromosomes revealed an independent nonsyntenic amplification of MYC and MDM2 on dmin in this tumor.

Adult↗