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PubMed2000

Progression of eIF4e gene amplification and overexpression in benign and malignant tumors of the head and neck.

BACKGROUND: The overexpression of eukaryotic initiation factor 4E (eIF4E) results in the up-regulation of gene products of mRNAs with long 5' untranslated regions (5' UTRs). The degree of gene amplification increases from the tumor free zone to the tumor core. This led the authors to hypothesize that the degree of eIF4E gene amplification and oncoprotein overexpression is progressive in the cells from normal head and neck tissue, to benign tumors, and eventually to invasive carcinomas (HNCA). METHODS: Using competitive polymerase chain reaction (PCR) and Western blot analysis, benign specimens from similar sites of 10 noncancer patients, 8 pleomorphic adenoma specimens, and 18 HNCA specimens were studied. DNA and protein extracts from each specimen were quantified for eIF4E gene copy number and level of eIF4E protein expression. RESULTS: There was no detectable eIF4E gene amplification and oncoprotein overexpression in benign tissue from noncancer patients (1.1 +/- 0.5 gene copy number [mean +/- standard deviation] and 0.9 +/- 0.5-fold protein elevation, respectively). Four of the eight pleomorphic adenomas analyzed showed eIF4E gene amplification of at least twofold, but none demonstrated protein elevation of any significance. In contrast, all HNCA specimens had detectable eIF4E gene amplification and protein overexpression. Furthermore, the mean degree of eIF4E gene amplification and overexpression was found to increase as cells from benign head and neck tissues (1.1 +/- 0.5 and 0.9 +/- 0.5), benign tumors (2.2 +/- 1.3 and 1.02 +/- 0.19), and HNCA (4.3 +/- 1.2 and 15.5 +/- 9.3) were compared. CONCLUSIONS: Progressive eIF4E gene amplification and overexpression were detected when normal tissues, benign tumors, and HNCA were compared. The degree of gene amplification and overexpression is variable within each tissue category. However, progression to malignant phenotype appears to be associated with an increasing degree of eIF4E gene amplification and overexpression.

Adenoma, Pleomorphic↗

PubMed2000

Formation of circular amplifications in Saccharomyces cerevisiae by a breakage-fusion-bridge mechanism.

Primary gene amplification, the mutation from one gene copy per genome to two or more copies per genome, is a major mechanism of oncogene overexpression in human cancers. Analysis of the structures of amplifications can provide important evidence about the mechanism of amplification formation. We report here the analysis of the structures of four independent spontaneous circular amplifications of ADH4:CUP1 in the yeast Saccharomyces cerevisiae. The structures of all four amplifications are consistent with their formation by a breakage-fusion-bridge (BFB) mechanism. All four of these amplifications include a centromere as predicted by the BFB model. All four of the amplifications have a novel joint located between the amplified DNA and the telomere, which results in a dicentric chromosome, and is adjacent to all the copies of the amplified DNA as predicted by the BFB model. In addition we demonstrated that two of the amplifications contain most of chromosome VII in an unrearranged form in a 1:1 ratio with the normal copy of chromosome VII, again consistent with the predictions of the BFB model. Finally, all four amplifications are circular, one stable endpoint for molecules after breakage- fusion-bridge.

Carrier Proteins↗

PubMed2000

Mutations in RAD3, MSH2, and RAD52 affect the rate of gene amplification in the yeast Saccharomyces cerevisiae.

We report here the use of the ADH4:CUP1 amplification detection system to identify five high amplification rate (HAR) strains of Saccharomyces cerevisiae that display 40- to 600-fold higher amplification rates than those of parental strains. We have identified a mutation in RAD3 DNA repair helicase gene in HAR strain B9-40 that results in a 40-fold increase in amplification rate. RAD3 is the functional homolog of the human XPD gene, suggesting that this model system will provide important candidates for genes that affect gene amplification in human cells. Isolation of the HAR strains has allowed us to test whether RAD52, which is essential for recombinational repair of DNA double-strand breaks, is also essential for amplification. Deletion of RAD52 in HAR strains B3-10 and B11-60 decreases amplification approximately 100-fold. In contrast, deletion of MSH2, which increases recombination between sequences with limited similarity, increases the amplification rate about 10-fold. These results suggest that recombination is an important step in amplification.

Adenosine Triphosphatases↗

PubMed2005

Amplification of c-erbB2 oncogene: a major prognostic indicator in uterine serous papillary carcinoma.

BACKGROUND: Overexpression of the epidermal growth factor type II receptor HER-2/neu has been associated with resistance to chemotherapy and poor survival in several human tumors. In the current study, the authors have determined the frequency and clinical significance of HER-2/neu gene amplification in uterine serous papillary endometrial carcinoma (USPC), a highly aggressive variant of endometrial carcinoma. METHODS: Fluorescence in situ hybridization (FISH) assay was used to analyze gene amplification in paraffin blocks from 30 women harboring Stage IA-IV USPC treated at the University of Arkansas for Medical Sciences (Little Rock, AR) from 1997 to 2004. Chromosome 17 polysomy status by FISH was also assessed in all specimens. USPC patient survival in relation to HER-2/neu gene amplification was analyzed using Kaplan-Meier curves in conjunction with the log-rank test. RESULTS: Amplification of the HER-2/neu gene by FISH was observed in 14 of the 30 (47%) cases. Heterogeneity was noted in 4 of 14 cases in the amplification of the HER-2/neu gene within the same tumor samples with pockets of amplified tumor cells amidst nonamplified tumor cells. Patients with USPC harboring tumors with HER-2/neu gene amplification had a significantly shorter survival time from diagnosis to disease-related death when compared with FISH-negative patients (P = 0.0008). African-American (AA) patients were found to have a poorer prognosis compared with Caucasian (C) women (P = 0.01) and to harbor USPC with significantly higher levels of HER-2/neu gene amplification (P = 0.02). CONCLUSIONS: HER-2/neu gene amplification in USPC was found to be an important prognostic indicator for poor outcome that occurs more frequently in AA when compared with C patients. Determination of HER-2/neu gene amplification may guide clinical management of patients with USPC and may have important implications for the implementation of novel treatment strategies.

Age Factors↗

PubMed1995

MDM2 gene amplification in bone and soft-tissue tumors: association with tumor progression in differentiated adipose-tissue tumors.

We have studied 107 bone and soft-tissue sarcomas and 8 lipomas for amplification of the MDM2 gene. This gene was amplified in 3 out of 67 osteosarcomas, 3 out of 20 malignant fibrous histiocytomas, 4 out of 20 liposarcomas, and 4 out of 8 lipomas. The amplification was associated with overexpression of mRNA. In osteosarcomas, contrary to previous findings, all amplifications were observed in primary lesions. In liposarcomas, the amplification was seen exclusively in well-differentiated tumors with high frequency (4/5) but not in other subtypes (0/15). In addition, MDM2 amplification was also frequently found in deep-seated intra- or intermuscular lipomas (4/5). Hence, it is suggested that MDM2 amplification plays a significant role in the development of differentiated adipose-tissue tumors. Three well-differentiated liposarcomas with MDM2 amplification coexisted with high-grade dedifferentiated sarcomas, in which MDM2 amplification was also observed. Interestingly, in 2 of these cases, the grades of amplification correlated with the histological grades, indicating an important role of MDM2 overexpression in tumor progression.

Adolescent↗

PubMed2005

Amplification of genes encoding KIT, PDGFRalpha and VEGFR2 receptor tyrosine kinases is frequent in glioblastoma multiforme.

KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs) are important clinical targets for tyrosine kinase inhibitors. The frequency of KIT and VEGFR2 amplification in glioblastomas is not known, and few data are available in any other human tumour type. We investigated 43 primary glioblastomas for KIT, VEGFR2, PDGFRA and EGFR amplification using fluorescence in situ hybridization. KIT was amplified in 47% and VEGFR2 in 39% of the glioblastomas, respectively, and PDGFRA in 29%. Thirty-five (81%) of the tumours had either KIT or EGFR amplification. KIT, PDGFRA and VEGFR2 amplifications were strongly associated (p < 0.0001 for each pairwise comparison), suggesting co-amplification, whereas no significant association was found with EGFR amplification. The four secondary glioblastomas arising from pre-existing lower grade astrocytic tumours investigated had KIT amplification but none had EGFR amplification. No mutations were detected with denaturing high-performance liquid chromatography in KIT exons 9, 11, 13 or 17, PDGFRA exons 12 and 18, or EGFR exons 18, 19 or 21. Glioblastomas with KIT, PDGFR or VEGFR2 amplification were associated with similar outcome to other glioblastomas. We conclude that KIT, PDGFRA and VEGFR2 are commonly amplified in primary glioblastoma and that they may also be amplified in secondary glioblastoma. Amplified kinases may be potential targets for tyrosine kinase inhibitor therapy.

Adult↗

PubMed2006

EGFR amplification and lack of activating mutations in metaplastic breast carcinomas.

Metaplastic breast carcinomas are reported to harbour epidermal growth factor receptor (EGFR) overexpression in up to 80% of the cases, but EGFR gene amplification is the underlying genetic mechanism in around one-third of these. In this study, EGFR gene amplification as defined by chromogenic in situ hybridization and protein overexpression was examined in a cohort of 47 metaplastic breast carcinomas. Furthermore, the presence of activating EGFR mutations in exons 18, 19, 20, and 21 was investigated. Thirty-two cases showed EGFR overexpression and of these, 11 (34%) harboured EGFR gene amplification. In addition, EGFR amplification showed a statistically significant association with EGFR overexpression (p < 0.0094) and was restricted to carcinomas with homologous metaplasia. Ten cases, five with and five without EGFR amplification, were subjected to microarray-based CGH, which demonstrated that EGFR copy number gain may occur by amplification of a discrete genomic region or by gains of the short arm of chromosome 7 with a breakpoint near the EGFR gene locus, the minimal region of amplification mapping to EGFR, LANCL2, and SEC61G. No activating EGFR mutations were identified, suggesting that this is unlikely to be a common alternative underlying genetic mechanism for EGFR expression in metaplastic breast carcinomas. Given that metaplastic breast carcinomas are resistant to conventional chemotherapy or hormone therapy regimens and that tumours with EGFR amplification are reported to be sensitive to EGFR tyrosine kinase inhibitors, these findings indicate that further studies are warranted to explore EGFR tyrosine kinase inhibitors as potential therapeutic agents for metaplastic breast carcinomas harbouring amplification of 7p11.2.

Breast Neoplasms↗

PubMed1999

Fluorescence in situ hybridization study of HER-2/neu oncogene amplification in prostate cancer.

Prostate cancer is a serious disease affecting men worldwide and treatment compromises the quality of life of prostate cancer patients. We conducted a study of 88 cases of prostate cancer in an attempt to identify prognostic biomarkers that can distinguish aggressive cases that must be treated immediately. HER-2/neu oncogene amplification was initially studied because amplification of this gene has been reported in many other cancers, including those studied in this laboratory. Fluorescence in situ hybridization (FISH) using a HER-2/neu gene probe with a chromosome 17 centromere control probe was performed on formalin-fixed, paraffin-embedded tissues. Of a total of 86 cases successfully analyzed, only 8 (9.3%) were found to be amplified. This frequency was lower than the frequency of amplification found in other cancers studied. Furthermore, no case was found where the level of amplification can be considered high. Only one case was found to have moderate amplification. The rest of the positive cases can all be classified as low amplification. Thus, while we have demonstrated that FISH is a sensitive technique for detecting oncogene amplification, the frequency and level of HER-2/neu amplification detected in prostate cancer seem to be lower than those in most cancers that we studied. In view of the fact that HER-2/neu amplification does not seem to play as significant a role, exploration of other biomarkers in prostate cancer is warranted.

Aged↗

PubMed1999

HER-2/neu oncogene amplification in stage I and stage III ovarian papillary serous carcinoma.

Oncogene amplification has been implicated in the genesis and progression of many cancers. Overexpression of the HER-2/neu proto-oncogene occurs in 20-30% of ovarian epithelial cancers, in which it may be of prognostic significance. Oncogene overexpression is traditionally studied using immunohistochemistry. In this study we used fluorescent in situ hybridization (FISH) to determine HER-2/neu amplification in ovarian papillary serous carcinoma and compared the frequency of amplification in two stages of the disease. Archival tissues from 23 cases of papillary serous ovarian carcinoma (9 cases of stage I and 14 cases of stage III) were analyzed by FISH using a HER-2/neu probe and a chromosome 17 centromere control probe. Determination of the level of amplification was performed according to the standard protocols of the Cytogenetics Laboratory at Rhode Island Hospital. Of the 23 cases successfully analyzed, the frequency of amplification among stage I tumors was 22% (2/9) and the frequency of amplification among stage III tumors was 71% (10/14). These results are significant (P = 0.036). The frequency of stage I tumors among amplified cases was 17% (27/12) and the frequency of stage III tumors among amplified cases was 83% (10/12). This study not only confirms the presence of a subset of ovarian papillary serous carcinoma with HER-2/neu gene amplification, but it also indicates that HER-2/neu oncogene amplification is more likely to be associated with a more advanced stage. Thus, the present data are consistent with the hypothesis that HER-2/neu amplification, similar to HER-2/neu protein over expression, is a prognostic marker of poor outcome.

Adult↗

PubMed1996

Amplification of the cyclin-dependent kinase 4 (CDK4) gene is associated with high cdk4 protein levels in glioblastoma multiforme.

Genetic alterations on the long arm of chromosome 12, including both gene amplification and allelic loss, are associated with malignant progression of human gliomas. The region of the chromosomal arm 12q that is amplified in malignant gliomas contains the CDK4 gene, a cell cycle regulatory gene which promotes cell division. To evaluate the frequency of CDK4 gene amplification, we analyzed a series of 355 brain tumors using a quantitative non-radioactive polymerase chain reaction assay. CDK4 gene amplification occurred in 9 of 81 glioblastomas (11%), but was rare in other neoplasms, including low-grade and anaplastic gliomas, meningiomas, medulloblastomas and metastatic carcinomas (only 6 of 274 cases). There was no correlation between CDK4 gene amplification and allelic loss of chromosome 12. To assess the significance of CDK4 gene amplification, we analyzed protein extracts from 37 glioblastomas by Western blotting with a commercially available polyclonal antibody to cdk4. All tumors with CDK4 gene amplification showed high cdk4 expression levels, whereas no increased cdk4 expression was seen in glioblastomas without CDK4 gene amplification. These data support the functional activity of CDK4 gene amplification in glioblastoma multiforme and point to an important role of CDK4 gene amplification in a subset of glioblastomas.

Brain Neoplasms↗

PubMed1997

Amplification of growth factor receptor genes and DNA ploidy pattern in the progression of gastric cancer.

To study the background of oncogene amplification in gastric cancers, we examined the correlation between occurrence of oncogene amplification and DNA ploidy pattern. In 57 primary gastric cancers, amplifications of c-erbB, c-erbB-2, c-met and K-sam genes were investigated by Southern blot analysis, and the DNA ploidy pattern was determined by static cytofluorometry and by flow cytometry. Oncogene amplification was detected in 11 cancers, 10 of which were advanced gastric cancers and 1 was an early differentiated type. The amplification of c-erbB-2 and K-sam genes was found exclusively in differentiated- and undifferentiated-type cancers, respectively. Of the 11 cancers, 5 were DNA-diploid and 6 were DNA-aneuploid. All the 11 tumours with oncogene amplification contained polyploid cell populations (polyploidy), whereas none of the tumours without polyploidy showed oncogene amplification. In differentiated-type cancers the incidence of polyploidy was high in both early and advanced stages, while in undifferentiated-type cancers it was low in early stages but significantly higher in advanced stages. It was shown that amplification of growth factor receptor genes is closely related to the presence of polyploidy, irrespective of any different stemline DNA-ploidy mode. The time-course of oncogene amplification and kinds of genes amplified may differ between differentiated- and undifferentiated-type gastric cancers.

Adenocarcinoma↗

PubMed1994

Estradiol receptors in combination with neu or myc oncogene amplifications might define new subtypes of breast cancer.

Amplifications of neu and c-myc were evaluated in 218 and 145 breast cancers (BC), respectively. Oncogene amplifications were determined for the most part by Southern blot. An association between the proportion of nodes affected and the intensity of neu amplification in estadiol receptor negative (ER-) BC was found (P = 0.028), which was confirmed by the multi-factor analysis of variance (P = 0.05). A significantly greater incidence in neu amplifications among BC with metastases was also found (P = 0.031). A strong association (P = 0.01) between the neu and myc amplification was observed. There is a strong association between myc amplification and ER- BC (P < 0.01). It is concluded that (1) the combination ER- with neu amplification might define a new group of more aggressive BC, as is suggested by their associated nodal involvement; (2) the linkage of myc amplifications with ER- BC and high grade of neu amplification might reflect a trait of tumor aggressivity.

Adult↗

PubMed1986

Gene amplification in human neuroblastomas: basic mechanisms and clinical implications.

Extrachromosomal double minutes (DM) and homogeneously staining regions (HSR) of metaphase chromosomes have been reported frequently in human neuroblastomas and tumor derived cell lines. We and other investigators have determined that virtually all DM- and HSR-bearing neuroblastoma cell lines have multiple copies of the oncogene N-myc. Circumstantial evidence suggests that the extrachromosomal DM may be the level at which amplification takes place, with subsequent linear integration into HSR. Indeed, DM may represent circular molecules. The global organization and fine structure of the amplified sequences remains to be determined, but the unit of amplification is probably between 2 X 10(5) and 2 X 10(6) base pairs (bp). In some cases, the process of amplification may involve somatic recombination with distant DNA segments. We have determined that N-myc amplification is a common finding in primary neuroblastomas from untreated patients. We identified N-myc amplification, ranging from 3- to 300-fold, in 34 of 89 cases (38%). N-myc amplification is found almost exclusively in tumors from patients with advanced stages of disease (stages III and IV, p less than 0.01). In addition, the presence of amplification is highly correlated with rapid tumor progression (p less than 0.001). Thus, amplification of the N-myc oncogene is a new intrastage prognostic factor, and N-myc amplification appears to play an important role in determining disease progression.

Cell Line↗

PubMed2026

Identification and characterization of ectopic chromosomal amplifications in acute myeloid leukemia cell limes using high-throughput chromosome conformation capture screening.

Despite advanced molecular diagnostics, improving outcomes for refractory acute myeloid leukemia (AML) remains challenging. Although many cancer-related genes are identified, their molecular mechanisms are not fully elucidated. Amplification is a mechanism of cancer-associated gene activation, and ectopic gene amplification may have particularly high pathological significance. However, research on ectopically amplified cancer-associated genes in leukemia remains limited. Here, we evaluated the usefulness of high-throughput chromosomal conformation capture (Hi-C) as a screening method for ectopic gene amplification and assessed whether ectopic amplification of cancer-associated genes may represent a general phenomenon in AML. We screened the U-937 and NB-4 cell lines using in situ Hi-C. Regions appearing as "high-intensity bands" in Hi-C contact maps were identified and validated using fluorescence in situ hybridization (FISH). Additionally, copy number variation analysis was performed using whole-genome sequencing (WGS) to extract cancer-associated genes with ectopic amplification. In the U-937, three genomic regions showing "high-intensity bands" were identified and confirmed as ectopic amplifications-including PDCD1LG2 (PD-L2), CD274 (PD-L1), and JAK2; that is, four copies were detected by WGS, and amplification signals were observed by FISH. In the NB-4, four such regions were detected, including MYC and KRAS, with expression level of 498 transcripts per million (TPM) and 34 TPM, respectively. Copy number variation analysis further identified multiple cancer-associated genes with ectopic amplification. Overall, these findings demonstrate the presence of ectopic amplification of cancer-associated genes in AML cell lines and support the usefulness of Hi-C as a screening method for detecting such genomic alterations.

Acute myeloid leukemia↗

PubMed2006

Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with clinicopathological features.

Amplification of chromosomal region 11q13 is one of the genetic alterations most frequently observed in oral squamous cell carcinoma (OSCC). Both TAOS1, a recently identified gene, and EMS1 were thought as two important target oncogenes for driving 11q13 amplification, and their contributions to oral carcinogenesis were hypothesized. Therefore we investigated amplifications of TAOS1 and EMS1 genes and their relations to clinicopathological variables in premalignant lesions (leukoplakias) and primary OSCC. TAOS1 amplification, beginning from mild-dysplastic epithelia, occurred in 33.3% of leukoplakias and 51.5% of OSCC. EMS1 amplification, beginning from moderate-dysplastic epithelia, occurred in 20% of leukoplakias and 57.6% of OSCC. Both gene amplifications were significantly related to different stages of oral carcinogenesis (p<0.05). During multistage carcinogenesis, no gene amplification was observed in normal tissue and non-dysplastic leukoplakias while, in OSCC with metastasis, amplification frequency increased significantly (p<0.005). Both TAOS1 and EMS1 amplifications were significantly associated with larger tumor size, presence of lymph node metastasis, poor histological differentiation and advanced clinical stage. Our data suggested potential roles in oral carcinogenesis and that TAOS1 might be involved earlier than EMS1. Both genes might be candidate biomarkers for diagnosis and prognosis in OSCC.

Adult↗

PubMed2006

[Detection of nasal colonization methicillin-resistant Staphylococcus aureus: a prospective study comparing real-time genic amplification assay vs selective chromogenic media].

UNLABELLED: In contrast to "classical" genic amplification, real-time genic amplification can be performed in every laboratory without the need of sophisticated isolation procedures. Moreover, real-time genic amplification allows an early detection of meticillin resistant Staphylococcus aureus colonization, 2 hours compared to 1 or 2 days for culture. OBJECTIVE: In order to assess the feasibility on Smartcycler of the IDI-MRSA real-time genic amplification assay in comparison with chromogenic media. METHODS: A prospective study has been initiated in July 2004: nasal swabs were taken from patients entering the ICU, vascular surgery, diabetology and geriatry wards. During a 4 months period, 682 specimens have been obtained from 508 patients. RESULTS: Sixty-four (9.3%) patients were positive by genic amplification and selective agar culture (CHROMagar MRSA, MRSASelect and/or ORSAB), 19 (2.9%) were positive by genic amplification only (3 of these patients were under antibiotic treatment); 572 specimens remained negative by both methods. The sensitivity and specificity of this assay were 100% and 96% respectively with a positive predictive value of 70% and negative predictive value of 100%. Initially 82 nasal specimens were unresolved (12%). 38 were resolved following a freeze-thaw cycle. Thus, 44 (6.4%) were unresolved specimens. Comparison between CHROMagar MRSA and MRSASelect showed a good correlation for the detection at 24 hours (5.5% and 5.6% respectively). These two chromogenic media allowed a much better detection of MRSA than ORSAB medium within 24H. CONCLUSION: The results obtained by the early real-time genic amplification for the detection of meticillin resistant Staphylococcus aureus are promising. Despite 6.4% amplification failure, we consider that IDI-MRSA real-time genic amplification assay represents a significant breakthrough in the detection of colonization.

Culture Media↗

PubMed2005

Oncogene amplification in transforming myelodysplasia.

The MLL gene, located within band 11q23, has been shown to be involved in translocations with a large variety of reciprocal sites in both lymphoid and myeloid leukemia and has also been shown to undergo submicroscopic self-fusion/partial duplication. We report 29 patients with cytogenetic evidence of 11q23 alteration, all of which demonstrate molecular cytogenetic evidence of amplification of the MLL gene by fluorescence in situ hybridization (FISH). In all MLL cases, the patients were clinically classified as having transforming myelodysplasia (RAEB/RAEBT) or AML. An additional patient with AML was found by 24-color and gene-specific FISH to have AML1 oncogene amplification. Four patients had been previously diagnosed with cancer and had received topoisomerase II targeted drug therapy which is known to be associated with fusion transcripts involving the MLL and AML1 genes. MLL amplification appeared in various forms: an atypical banded region that bridges from 11q23 into a dicentric chromosome, expanded regions emanating from band 11q23, chromosome 11 paint-positive rings with "spoke-like" MLL amplification, and expansion at sites other than chromosome 11 (including extra markers) in the absence of one of the 11 homologues. The fluorescence pattern in most cases suggests palindromic duplication with neighboring sequences in the long arm of chromosome 11. As opposed to MYCN amplification in hsrs (homogeneously staining regions) and double minutes in neuroblastoma, amplification of MLL in most cases occurred at the site of the gene. All of our patients rapidly developed refractory AML. The frequency and clinical correlations of MLL gene amplification in leukemia will need careful follow-up, since the frequently cryptic amplification described in these cases may not generally provoke confirmatory FISH studies. The reported MLL cases represented about 1% of the total abnormal MDS/AML cases over 8 years. A common cytogenetic profile of 5 q-, -17/17 p-, -18/18 q-, and a missing or abnormal chromosome 11, may help direct appropriate follow-up studies. The MLL and the AML1 oncogenes appear to be the only oncogenes amplified at the natural site of the gene. Both genes also show a high degree of diversity of pathogenic mechanisms of leukemia evolution, including numerous reciprocal fusion genes in transformation to either AML or ALL and gain of function amplification.

Adult↗

PubMed2004

[CCND1 gene amplification in the adenoid cystic carcinoma of the minor salivary glands].

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumour of epithelial origin that represents the most common malignant neoplasm of the minor salivary glands. However, little is known about the genes involved in the development and progression of this tumour. Cyclin D1 gene (CCND1) plays a key role in the control of the cell cycle, and its amplification is described in numerous cancers. The aim of this study is to determine the amplification of the CCND1 gene in the ACC of the minor salivary glands. MATERIALS AND METHODS: A retrospective study was performed on 12 patients with ACC of the head and neck. The amplification of the CCND1 was determined using multiple PCR. RESULTS: Amplification of the CCND1 was found in 4 patients (33.3%). No correlation was found between CCND1 amplification and clinicopathological parameters, although disease-free survival was diminished in patients with amplification. DISCUSSION/CONCLUSIONS: Our study demonstrates for the first time the amplification of the CCND1 gene in ACC. We have found an amplification rate similar to others neoplasms. CCND1 amplification seems to be associated with a poorer prognosis in these tumours, although this needs to be confirmed in larger studies.

Adult↗