Disease relevance of Gene Amplification

• Using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the RNAase A mismatch cleavage method, we have examined c-K-ras genes in human pancreatic carcinomas [1].
• We show here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification [2].
• In human soft tissue sarcomas, inactivation apparently results from MDM2 gene amplification [3].
• The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-31 is designed to test the advantage of adding Herceptin to the adjuvant chemotherapeutic regimen of doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) in the treatment of stage II breast cancer with HER2 overexpression or gene amplification [4].
• Overexpression of the EGF receptor gene in A431 epidermoid carcinoma cells is due to gene amplification [5].

High impact information on Gene Amplification

• Induction of Ras and Raf can be caused by active N-Ras and B-Raf mutants as well as by gene amplification [6].
• Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles [7].
• This study examines whether alterations of one or both p53 alleles were sufficient to allow gene amplification to occur [8].
• We propose that, in the initial event of CAD gene amplification, much of the short arm is transferred from one B9 chromosome to another [9].
• The probe detects gene amplification in Na+/H+ antiporter "overexpressers" and a single class of mRNA of ca. 5.6 kb in human, mouse, and hamster cells [10].

Chemical compound and disease context of Gene Amplification

• Plasmid-determined tetracycline resistance in Streptococcus faecalis: evidence for gene amplification during growth in presence of tetracycline [11].
• Androgen receptor gene amplification: a possible molecular mechanism for androgen deprivation therapy failure in prostate cancer [12].
• Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials [13].
• These results indicate that the increased adenosine deaminase activity in deoxycoformycin-resistant rat hepatoma cells is due in large part, but not exclusively, to gene amplification [14].
• Two of 17 carcinomas showing cyclin D1 expression in more than 5% of neoplastic cells, but without gene amplification, were found to harbor single-base substitutions in CCND1 that changed proline 287 into threonine and serine, respectively [15].

Biological context of Gene Amplification

• Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53 [8].
• Identification of DNA sequence responsible for 5-bromodeoxyuridine-induced gene amplification [16].
• ORC binding, gene amplification, and the nature of metazoan replication origins [17].
• This phenotype is characterized by overexpression of P-glycoprotein without an increase in P-glycoprotein messenger RNA or gene amplification; increased glutathione S-transferase (GST) activity; and resistance to vincristine, colchicine, and etoposide but not to doxorubicin [18].
• Prognostic factor analysis indicated that NMYC gene amplification and an elevated serum lactate dehydrogenase level were statistically significant markers of higher risk disease within the diploid group (two-sided P values of .005 and .003, respectively) [19].

Anatomical context of Gene Amplification

• Using previously isolated mouse L-cell transferents for the human T-cell differentiation antigen Leu-2, we now report the first example of spontaneous gene amplification for membrane antigens [20].
• Early dihydrofolate reductase gene amplification events in CHO cells usually occur on the same chromosome arm as the original locus [21].
• We isolated mutations in Drosophila E2F and DP that affect chorion gene amplification and ORC2 localization in the follicle cells [22].
• 3-Hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) is an abundant protein of the crystalloid endoplasmic reticulum of UT-1 cells, a line of cultured hamster cells that over-produces the reductase as a result of gene amplification [23].
• Similarly, selection of infected 3T3 fibroblasts for Ada gene amplification yielded a 20-fold increase in FVIII expression [24].

Associations of Gene Amplification with chemical compounds

• Normal and LFS cells containing wild-type p53 arrested in G1 when challenged with the uridine biosynthesis inhibitor PALA and did not undergo PALA-selected gene amplification [7].
• METHODS: Formalin-fixed, paraffin-embedded tumor tissue samples were used for Agno gene amplification and for immunohistochemical analysis [25].
• This system was first characterized by visualization of chromosome homogeneously staining regions (HSRs) produced by gene amplification using a dihydrofolate reductase (DHFR) expression vector with methotrexate selection [26].
• Exposure of Chinese hamster cells to reduced oxygen partial pressure results in a marked enhancement in the frequency of methotrexate resistance and dihydrofolate reductase gene amplification [27].
• To study the effect of apoptosis on gene amplification, we have constructed HeLa S3 cell lines in which the expression of bcl-2 (BCL2) can be controlled by tetracycline in the growth medium [28].

Gene context of Gene Amplification

• Furthermore, the normal function of p53 may be abrogated by MDM2 (murine double minute-2) gene amplification in some human tumors [29].
• Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas [30].
• These observations, in particular PBP gene amplification, suggest that PBP, by its ability to function as ERalpha coactivator, might play a role in mammary epithelial differentiation and in breast carcinogenesis [31].
• The finding of an amplicon at 8p22-23 resulting in CTSB gene amplification and overexpression supports an important role for CTSB in esophageal adenocarcinoma and possibly in other tumors [32].
• In individual cell lines showing gene amplification, the copy number of each of the three mdr genes was identical, suggesting that the three mdr genes became amplified as part of a single amplicon in these cells [33].

Analytical, diagnostic and therapeutic context of Gene Amplification

• MATERIALS AND METHODS: HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry [34].
• Western blot analysis of the EGF-R protein revealed high levels of a truncated EGF-R protein in two of the four tumors with EGF-R gene amplification [35].
• In addition, ID2 mRNA expression was not associated with MYCN gene amplification status (P = 0.15) or MYCN expression (r = 0.22) in 131 separate diagnostic primary neuroblastoma samples analyzed by real-time quantitative RT-PCR [36].
• The growth of U87 MG xenografts, a glioma cell line that endogenously expresses approximately 10(5) EGFRs in the absence of gene amplification, was not inhibited by mAb 806 [37].
• Previous studies have demonstrated the usefulness of flow cytometry in the analysis of dihydrofolate reductase (EC 1.5.1.3) gene amplification [38].

References