SEARCH · PubMed Health

Results for “MYC amplification”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed2001

[Clinical significance of c-myc oncogene amplification in primary hepatocellular carcinoma by interphase fluorescence in situ hybridization].

OBJECTIVE: To investigate the relationships between c-myc oncogene amplification in primary hepatocellular carcinoma (HCC) and its clinical prognosis. METHODS: To detect c-myc oncogene amplification in 100 cases with primary HCC and in 6 cases with satellite nodes by interphase fluorescence in situ hybridization (FISH). RESULTS: c-myc amplification was detected in 92 of 100 (92%) cases with HCC, 37 of which (37%) showed high copy amplification (HC), 55 (55%) low copy amplification (LC) and 8 (8%) single copy or no amplification (SC). There wasn't statistically different significance between the frequency of c-myc amplification and clinical stage and tumor size, and pathological types (P > 0.05), however, in the 90 follow-up resected cases, the one-year rates of recurrence in HC, LC and SC were 70.6% (24/34), 39.6% (19/48) and 12.5% (1/8) respectively (P < 0.05) but the recurrence rates after more than one year were 14.70% (5/34), 14.6% (7/48) and 0 (0/8) respectively (P > 0.05). Meanwhile, two-year survival rate of patients with HC was significantly lower in comparison with those with LC and SC (P = 0.001). CONCLUSIONS: There is a high frequency of c-myc oncogene amplification in primary HCC and the fact that the patients with HC showed poorer prognosis indicates that the level of c-myc oncogene amplification may be a sensitive index in the prognosis of HCC.

Adult↗

PubMed1996

Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.

PURPOSE: In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions. METHODS: Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region. RESULTS: In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage. CONCLUSION: The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.

Antibodies, Monoclonal↗

PubMed1986

Clinical implications of oncogene activation in human neuroblastomas.

Amplification of the oncogene N-myc has been identified in almost all human neuroblastoma cell lines tested. Eighty-nine primary neuroblastomas from untreated patients were studied to determine the frequency and clinical significance of N-myc amplification. Tumor DNA was analyzed by hybridization with the radiolabeled probe pNB-1 for N-myc. Amplification (3-300 copies) of the N-myc gene was found in 34 of the 89 tumors (38%). Amplification was not found in 8 Stage I or 5 Stage IV-S tumors, but it was found in 2 of 16 with Stage II, 13 of 20 with Stage III, and 19 of 40 with Stage IV tumors (P less than 0.01). Correlation of N-myc amplification with progression-free survival (PFS) indicated that N-myc amplification was associated with a worse prognosis (P less than 0.0001). The PFS at 18 months was 70%, 30%, and 5% for patients whose tumors had 1, 3-10, and more than 10 copies, respectively. Even within individual stages, the presence of N-myc amplification correlated with rapid progression. For instance, of 16 patients with Stage II disease, the 2 with N-myc amplification developed progressive disease rapidly, whereas only 1 of 14 without amplification progressed (P = 0.03). Similarly, those with Stage III and IV disease whose tumors have multiple copies of N-myc had a substantially worse prognosis. The correlation between N-myc amplification and age at diagnosis was also analyzed. Although N-myc amplification was detected in only 4 of 28 infants less than 1 year of age, compared to 30 of 61 older patients (P less than 0.005), this difference disappeared when corrected for disease stage. The results suggest that N-myc amplification is a powerful prognostic indicator, and that this gene may play an important role in the progression of certain neuroblastomas.

Age Factors↗

PubMed1988

Surgical aspects of N-myc oncogene amplification of neuroblastoma.

The surgical aspects of N-myc oncogene amplification of neuroblastic tumors were studied in 42 patients with ganglioneuroblastoma or neuroblastoma. The cumulative survival rate of patients with fewer than 10 copies of N-myc (L group) was 73.7% 48 months after initiation of therapy, whereas the rate for those with more than 10 copies of N-myc (H group) was 0% by 20 months (P less than 0.000001). Clinical prognostic factors of neuroblastic tumors such as age, stage, histologic findings, and primary site correlated with the amplification of N-myc. N-myc amplification of more than 10 copies was evident in one of 16 (6.3%) patients less than 1 year of age and in 13 of 26 (50%) patients over 1 year of age and was detected in one of six tumors in stage II, four of 10 in stage III, seven of 16 in stage IV, and two of six in stage IV-S. The amplification occurred more frequently in patients with neuroblastoma than in those with ganglioneuroblastoma and was observed only in tumors of a suprarenal region. Preoperative chemotherapy was prescribed for 19 of the 26 patients with stage III or IV tumors and was similarly effective in both L and H groups. Ipsilateral nephrectomy or combined resection of a part of liver had to be performed in nine of 11 (82%) patients with stage III or IV tumors in the H group but in only one of 15 (6.7%) in the L group, thereby suggesting that the tumor with an amplified N-myc is more invasive. In patients in the advanced stage, total or nontotal resection of the tumor did not affect the survival in the L group, but the survival interval was prolonged significantly by the total removal of the tumor in patients in the H group. These data should aid in the surgical treatment of patients with poor-prognostic neuroblastoma and an amplified N-myc oncogene.

Child↗

PubMed1987

N-myc oncogene amplification and prognostic factors of neuroblastoma in children.

The N-myc oncogene of 28 neuroblastic tumors obtained from 16 untreated and 12 pretreated children was clinically evaluated and compared with known prognostic factors. Significant amplification of the N-myc (more than ten copies) was observed in 0 of 2 tumors in stage I, 1 of 5 in stage II, 2 of 6 in stage III, 6 of 9 in stage IV, and 2 of 6 in stage IVS. In stages II, III, IV, and IVS, all 15 patients with low N-myc amplification (under ten copies) are alive without disease, while among 11 patients with the amplification, seven died with progressive disease and two have a recurrence (P less than .01). All tumors with N-myc amplification originated from the suprarenal region and the amplification appeared in 55% of those from that origin. The amplification also correlated with the age factor. These results suggest that the genomic amplification of N-myc seems to be correlated with known prognostic factors of neuroblastoma, and may be a reliable factor even in the case of preoperatively treated tumors.

Age Factors↗

PubMed2001

[Correlation of c-myc gene amplification, MTS1/p16 gene alternation, and HBV infection in human hepatocellular carcinoma].

OBJECTIVE: To observe the roles of c-myc gene amplification, MTS1/p16 gene alternation, and HBV infection in the pathogenesis and progression of hepatocellular carcinoma (HCC). METHODS: A d-PCR-PAGE-laser scanning technique was used to define amplifications of c-myc oncogene. Alternations of MTS1/p16 gene exon1 and exon2 were analysed by PCR and single-strand conformation polymorphism (SSCP) silver stain method. HBV-DNA was assayed by PCR. RESULTS: (1)The positive rates of c-myc gene amplification of HCCs and their paired non-cancerous liver tissues were 44.83% (13/29) and 51.72% (15/29). The discrepancies between them were not significant (P>0.05), but they were both significantly higher than that of cirrhotic liver tissues (8.33%, 1/12, P<0.05). (2)A total of 3 homozygous deletions and no mutations of MTS1/p16 gene exon1 and exon2 in HCCs were found in the subset of HCCs. (3)The discrepancies of the positive rates of HBV-DNA among normal liver (14.29%, 2/14), cirrhotic liver (66.67%, 8/12) and HCCs (96.55%, 28/29) were significant (P<0.001). Moreover, the HBV-DNA positive rates increased according to the development of liver lesions (b=0.3986, P<0.001). CONCLUSIONS: (1)C-myc gene amplification and HBV infection are closely related to the development and progression in a subset of HCCs. However, c-myc gene amplification does not correlate with the HBV infection in HCCs. (2)The homozygous deletions and mutations of MTS1/p16 gene are infrequently encountered in the subset of HCCs.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

c-myc gene amplification detected in preinvasive intraepithelial cervical lesions.

The aim of the present work was to evaluate the c-myc gene amplification process in cervical samples and to analyze the relationship between the activation of this proto-oncogene and the cytologic and/or histologic status. Thirty-four normal cervical samples and 105 abnormal cervical tissue scrapes, previously used for PAP or histopathologic diagnosis, were analyzed for c-myc gene amplification. Detection of c-myc gene amplification was performed using a polymerase chain reaction (PCR)-based method known as target arbitrarily primed-PCR (TAP-PCR). For c-myc amplification, significant differences were found between normal samples and samples presenting different grades of lesions (P<0.001). A significant difference between high-grade squamous intraepithelial lesions (HG-SIL) and the other stages of cervical disease was also found (P<0.05). This study demonstrated that c-myc copy number increases according to the histologic grade of the lesion. These results could indicate that oncogene amplification takes place in preinvasive stages of cervical disease and could cooperate not only in tumor progression but also in cell transformation.

Carcinoma, Squamous Cell↗

PubMed1990

N-myc oncogene amplification in paediatric tumours.

DNA, extracted from tumours arising in 29 paediatric patients [14 neuroblastoma, 9 Wilms tumour (nephroblastoma), 6 miscellaneous] was investigated for evidence of N-myc amplification, using pNb-1, a recombinant plasmid containing a 1.0 Kb fragment homologous to the 5' end of the human N-myc gene. Within the neuroblastoma group, 4 patients had 15 or more copies of N-myc which correlated with advanced disease stage, and 3 other patients showed low grade amplification (2-5 copies). Low grade amplification was also observed in one patient with stage III unfavourable histology Wilms tumour, resistant to treatment. N-myc was present at single copy level in all other tumours studied. It is concluded that N-myc activation by amplification confers aggressive properties on a variety of embryonal tumours, rather than being restricted to initiation of neoplasia in tumours of neuroectodermal origin. A greater understanding of the complex interaction of a number of oncogenes involved in neuroblastoma may enable more effective therapeutic strategies to be devised.

Child↗

PubMed1989

c-myc gene amplification during hepatocarcinogenesis by a choline-devoid diet.

Liver tumors arise in rats fed a choline-devoid diet without added carcinogens. We found amplification of the c-myc gene in 13/13 of these tumors. The amplification ranged from 2- to 70-fold and was accompanied by an increase in c-myc gene expression. Amplification of c-myc was larger in tumors of rats fed a choline-devoid diet followed by a choline-supplemented diet than in tumors from animals fed a choline-devoid diet exclusively. In the former animals, low levels of c-myc gene amplification were also detected in nontumorous regions of tumor-bearing livers. The choline-devoid diet provides an in vivo experimental model for the induction of gene amplification in the rat liver. In this setting, amplification of the c-myc gene may be an early and critical event in carcinogenesis.

Animals↗

PubMed1992

Chromatin structure changes suggest a compensatory response to c-myc gene amplification in malignant fibrous histiocytoma.

Changes in chromatin structure as determined from DNAse I hypersensitive site analysis are associated with c-myc amplification and increased transcript/protein levels in malignant fibrous histiocytoma (MFH) cell lines. A DNAse I hypersensitive site near the PO promoter region was observed in one MFH cell line (UR HCL 1), and in normal fibroblasts (HFF), but not in an MFH cell line with an amplified c-myc gene (P3C). A DNAse I hypersensitive site exclusive to P3C amplified c-myc was identified slightly 3' of exon one. No alterations in c-myc DNAse I hypersensitive site patterns were observed in HFF fibroblasts following serum release, when peak levels of c-myc transcript were induced. DNAse I hypersensitive site patterns associated with gene amplification may reflect a compensatory response by P3C cells to an abundance of c-myc transcript. Furthermore, elevated levels of protein in P3C cells provide additional evidence that amplified c-myc is an oncogene in MFHs.

Chromatin↗

PubMed1992

Detection of N-myc gene amplification in bone marrow specimen of stage IV neuroblastoma patients.

N-myc gene amplification is an unfavorable prognostic factor in neuroblastoma; therefore, its detection might have therapeutical consequences. Because of the reliability of noninvasive diagnostic methods such as X-ray examination and measurement of vanilymandelic acid and the lack of technical unavailability at most institutions, the determination of the N-myc status of neuroblastoma often is not done. In our investigation of 14 neuroblastoma patients, we could demonstrate N-myc gene amplification in the bone marrow of 5 patients with neuroblastoma stage IV disease and in bone marrow infiltration without enrichment of neuroblastoma cells. Otherwise, no information about the tumor content of N-myc gene copies at the time of initial diagnosis could be obtained. At the subsequent resection, the N-myc gene amplification was confirmed by the additional Southern blot analysis and in situ hybridization of tumor tissue. Furthermore, the N-myc status of bone marrow was analyzed during the stages of chemotherapy in three cases.

Blotting, Northern↗

PubMedDate not supplied

C-myc gene amplification in different stages of oesophageal squamous cell carcinoma: prognostic value in relation to treatment modality.

BACKGROUND: The proto-oncogene c-myc is known to be involved in the regulation of proliferation, apoptosis and cell differentiation. MATERIALS AND METHODS: Amplification of c-myc was determined by means of differential PCR in 77 surgically treated stage I or II oesophageal squamous cell carcinomas (SCC) as well as in 43 locally advanced SCC (cT3-4 cN0-1 cM0) treated by radiochemotherapy and facultatively by surgery. The findings were correlated to overall survival and to response to radiochemotherapy. RESULTS: C-myc gene amplification was present in 8 out of 77 surgically treated SCC (10.4%) and in 13 out of 43 multimodally treated SCC (30.2%). Among the surgically treated tumours, the presence of c-myc amplification was correlated with high proliferative activity (p = 0.0399) but not with overall survival. Among the multimodally treated SCC, c-myc amplification tended to be correlated with response to chemotherapy and response to radiochemotherapy (not significant) whereas no impact on overall survival was found. CONCLUSION: Amplification of c-myc is found more frequently in advanced stages of oesophageal SCC than in early stages. C-myc amplification, however, does not influence the overall survival of oesophageal SCC patients treated either by surgery alone or by multimodal therapy.

Adult↗

PubMed1993

Determination of N-myc gene amplification in neuroblastoma by differential polymerase chain reaction.

Determination of N-myc gene amplification, a powerful prognostic indicator in the childhood tumour, neuroblastoma, has routinely been performed by Southern analysis. We have developed a differential polymerase chain reaction (PCR) assay, in which the N-myc target gene is co-amplified with a control gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Following electrophoresis, a ratio between the two PCR products within a given DNA sample is then determined by densitometry. This assay was applied to DNA isolated from 32 primary neuroblastoma tumours for which the N-myc status had previously been determined by Southern analysis. Following PCR, samples containing a single copy of the N-myc oncogene were clearly distinguishable from samples with N-myc gene amplification, based on an N-myc/GAPDH ratio of below or above 1.0, respectively. Linear regression indicated a highly significant relationship (R = 0.94; P < 0.0001) between N-myc copy number (Southern) and N-myc/GAPDH ratio (PCR). Serial dilution of N-myc amplified DNA with non-amplified control DNA indicated that the PCR assay was sufficiently sensitive to detect two-fold amplification. Moreover, such serial dilution allowed determination of N-myc copy number. The assay, which requires only small amounts of tissue and does not utilize 32P-radioactivity, therefore provides a rapid and sensitive alternative to Southern analysis.

Base Sequence↗

PubMed1999

Chromosome 8 copy numbers and the c-myc gene amplification in non-small cell lung cancer. Analysis by interphase cytogenetics.

Amplification of the c-myc gene has been reported in non-small cell lung cancer (NSCLC). We performed dual color fluorescence in situ hybridization (FISH) to detect amplifications of the c-myc gene on chromosome 8 to evaluate the relationship between these possible abnormalities and pathological stage. Tumor tissue samples were obtained from 29 patients of NSCLC in Stage I (n = 15) and III (n = 14) who underwent lobectomy at Saitama Cancer Center. Samples were analyzed for chromosome 8 centromere and c-myc gene by dual color FISH. The numerical aberration rate of chromosome 8 was 36.8 +/- 20.3% in Stage I and 40.6 +/- 24.8% in Stage III. The amplification rate of c-myc gene was 48.3 +/- 15.2% in Stage I and 57.4 +/- 17.0% in Stage III. There was a significnat difference in the numerical aberration rate of chromosome 8 between patients who survived for 5 years or more (28.8 +/- 17.5%) and those who survived less than 5 years (44.7 +/- 23.1%). The amplification rate of c-myc gene was not different between patients who survived more and less than 5 years survival, and who survived more and less than 3 years. The 5 year-survival rate in patients who showed 40% or more of chromosome 8 aberrations (n = 13) was 15.4%, which revealed significantly less than that of patients who showed less than 40% of aberrations (n = 16) (56.3%). There was no difference between the 5 year-survival rate in patients whose amplification rates of c-myc gene were equal or more than 50% (n = 16) and less than 50% (n = 13) (25.0% and 53.9%). The rate of chromosome 8 aberrations and the c-myc gene amplification rate were not correlated with pathological stage. However, the rate of chromosome 8 aberration showed correlation in terms of longevity of survival rate, therefore we considered the rate of chromosome 8 aberration to be an additional prognostic factor of patient with NSCLC.

Adult↗

PubMedDate not supplied

Detection of n-myc gene amplification in neuroblastoma by comparative, in situ,and real-time polymerase chain reaction.

We have used semiquantitative comparative and real-time quantitative polymerase chain reactions (PCR) to detect n-myc gene-amplification in 20 frozen neuroblastoma biopsies and IMR 32 cell line to predict biological behavior of the tumors. Two primer pairs were used for 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 analyses were 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-labeled fluorescent probe pair to detect the product. Calibration curve, set up from a serial dilution including samples with 1, 2, 10, 13, 25-fold n-myc oncogene amplification, was used for quantitative analysis. The semiquantitative method did not show distinct difference between tumor groups with no amplification and less than 10-fold amplification, whereas quantitative LightCycler analysis was able to detect even 2-fold amplification. Differentiated neuroblastomas seldom show n-myc amplification. In spite of this, we have found two partly differentiated tumor samples that contained n-myc amplification. In these cases in situ PCRs were performed to examine the tumor heterogeneity. We used biotinated ATP labeling and the same primer pair as for the LightCycler analysis. In both cases differentiated cells did not show n-myc gene amplification, whereas considerable amplification was detected in the neuroblasts.

Child↗

PubMed2002

C-myc oncogene amplification in ductal carcinoma in situ of the breast.

The c-myc oncogene is frequently activated in invasive breast cancer and has been associated with high nuclear grade, lymph node metastasis and poorer disease outcome. We have examined c-myc oncogene amplification using fluorescence in situ hybridization in a series of 96 pure DCIS. Additionally we assessed amplification and expression of the Her2 and bcl-2 oncogenes. The findings were compared with clinicopathological data, Ki-67 proliferative index and hormone receptor status. We observed c-myc oncogene amplification in 19 tumours (20%). These cases were significantly associated with an average of 38% higher proliferative activity (p = 0.045), a 43% larger tumour size (p = 0.029) and the otherwise rare micropapillary subtype (p = 0.0005). Concluding the c-myc oncogene appears to be involved in the development of a more aggressive phenotype of DCIS.

Adult↗

PubMed1996

DNA ploidy and MYC DNA amplification in ovarian carcinomas. Correlation with p53 and bcl-2 expression, proliferative activity and prognosis.

There is increasing evidence that DNA ploidy is a prognostic factor in ovarian carcinomas, but it is uncertain whether MYC DNA amplification is an epiphenomenon of DNA nondiploidy or a distinct biological change with an impact on the clinical course of the disease. To clarify these issues we analysed DNA ploidy by flow and image cytometry and MYC copy number by polymerase chain reaction in archival material from ovarian carcinomas with known follow up. The results were compared with proliferative activity (Ki67 index) and p53 and bcl-2 expression. DNA cytometry revealed nondiploidy in 84 of 144 cases (58.3%). Nondiploidy was statistically significantly correlated with histological tumour type, histological grade, Ki67 index > 10%, FIGO stage, presence of residual tumour after debulking surgery and adverse postoperative outcome. Furthermore, DNA nondiploidy was associated with p53 accumulation. We found that 84.9% of the p53-positive cases were nondiploid. This points to the paramount importance of wild type p53 for the maintenance of genome integrity in this tumour type. MYC DNA amplification was seen in 33.8% (26/77 cases) of ovarian carcinoma. There was no correlation between MYC DNA amplification and histological tumour type, histological grade, FIGO stage, DNA ploidy, proliferative activity or prognosis. However, when p53 and bcl-2 expression was taken into account, a statistically significant correlation between gene alteration or expression patterns and histological tumour type was revealed. The group of mucinous carcinomas demonstrated both MYC DNA amplification and strong bcl-2 expression in 50% and contained the largest fraction of cases without aberration (37.5%). Endometrioid carcinomas were characterized by strong bcl-2 expression in 85%, whereas serous and undifferentiated carcinomas predominantly exhibited p53 alterations, frequently accompanied by bcl-2 overexpression or MYC DNA amplification. Thus, in interaction with other genes MYC DNA amplification may play a role in the determination of the varying differentiation patterns of ovarian carcinomas.

Aged↗

PubMed1998

Epidermal growth factor-dependent cell cycle progression is altered in mammary epithelial cells that overexpress c-myc.

Amplification and overexpression of the c-myc gene are common in primary human breast cancers and have been correlated with highly proliferative tumors. Components of the epidermal growth factor (EGF) receptor signaling pathway are also often overexpressed and/or activated in human breast tumors, and transgenic mouse models have demonstrated that c-myc and transforming growth factor alpha (a member of the EGF family) strongly synergize to induce mammary tumors. These bitransgenic mammary tumors exhibit a higher proliferation rate than do tumors arising in single transgenics. We, therefore, chose to investigate EGF-dependent cell cycle progression in mouse and human mammary epithelial cells with constitutive c-myc expression. In both species, c-myc overexpression decreased the doubling time of mammary epithelial cells by approximately 6 h, compared to parental lines. The faster growth rate was not due to increased sensitivity to EGF but rather to a shortening of the G1 phase of the cell cycle following EGF-induced proliferation. In cells with exogenous c-myc expression, retinoblastoma (Rb) was constitutively hyperphosphorylated, regardless of whether the cells were growth-arrested by EGF withdrawal or were traversing the cell cycle following EGF stimulation. In contrast, the parental cells exhibited a typical Rb phosphorylation shift during G1 progression in response to EGF. The abnormal phosphorylation status of Rb in c-myc-overexpressing cells was associated with premature activation of cdk2 kinase activity, reduced p27 expression, and early onset of cyclin E expression. These results provide one explanation for the strong tumorigenic synergism between deregulated c-myc expression and EGF receptor signal transduction in the mammary tissue of transgenic mice. In addition, they suggest a possible tumorigenic mechanism for c-myc deregulation in human breast cancer.

Animals↗