Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma
The amplification of the MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of MYCN remains controversial. To reassess the clinical implications of MYCN amplification and expression in neuroblastoma, the status of...
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| creator | Tanaka, Shinji Tajiri, Tatsuro Noguchi, Shin-ichi Shono, Kumiko Ihara, Kenji Hara, Toshiro Suita, Sachiyo |
| description | The amplification of the
MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of
MYCN remains controversial. To reassess the clinical implications of
MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the
MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses.
Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (
MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of
MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 23 samples were analyzed for
MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (
MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method.
Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 46 samples showed
MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of
MYCN-amplified cells. The cases of
MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of >1 year at diagnosis [
P < .0001], nonmass screening [
P = .0003], advanced stage [
P < .0001], diploid or tetraploid [
P < .0001], and a Shimada unfavorable histology [
P < .0001]).
MYCN gene dosages of more than 2.0 were significantly associated with a high expression of
MYCN (
P = .0459). However, the expression level of
MYCN was not significantly associated with any other prognostic factors.
Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the
MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of
MYCN amplification. In this highly sensitive analysis,
MYCN amplification (
MYCN/p53 ≥ 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of
MYCN does not appear to be an independently significant prognosis factor. |
| doi_str_mv | 10.1016/j.jpedsurg.2003.09.015 |
| format | Article |
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MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of
MYCN remains controversial. To reassess the clinical implications of
MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the
MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses.
Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (
MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of
MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 23 samples were analyzed for
MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (
MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method.
Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 46 samples showed
MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of
MYCN-amplified cells. The cases of
MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of >1 year at diagnosis [
P < .0001], nonmass screening [
P = .0003], advanced stage [
P < .0001], diploid or tetraploid [
P < .0001], and a Shimada unfavorable histology [
P < .0001]).
MYCN gene dosages of more than 2.0 were significantly associated with a high expression of
MYCN (
P = .0459). However, the expression level of
MYCN was not significantly associated with any other prognostic factors.
Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the
MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of
MYCN amplification. In this highly sensitive analysis,
MYCN amplification (
MYCN/p53 ≥ 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of
MYCN does not appear to be an independently significant prognosis factor.</description><identifier>ISSN: 0022-3468</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1016/j.jpedsurg.2003.09.015</identifier><identifier>PMID: 14694373</identifier><identifier>CODEN: JPDSA3</identifier><language>eng</language><publisher>Philadelphia, PA: Elsevier Inc</publisher><subject>Biological and medical sciences ; Carbohydrates (enzymatic deficiencies). Glycogenosis ; Child ; Child, Preschool ; DNA - isolation & purification ; Errors of metabolism ; Female ; FISH ; Gene Amplification ; Gene Dosage ; Gene Expression ; General aspects ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Medical sciences ; Metabolic diseases ; MYCN ; N-Myc Proto-Oncogene Protein ; Neuroblastoma ; Neuroblastoma - genetics ; Neuroblastoma - metabolism ; Neurology ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Oncogene Proteins - genetics ; Oncogene Proteins - metabolism ; Polymerase Chain Reaction ; Prognosis ; quantitative polymerase chain reaction ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - genetics ; RNA - isolation & purification ; RNA - metabolism ; Tumors of the nervous system. Phacomatoses</subject><ispartof>Journal of pediatric surgery, 2004, Vol.39 (1), p.63-68</ispartof><rights>2004 Elsevier Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-5430d5374bce604701c8f1bf81ea30b3ec19826c30933791416e20061bbd6c423</citedby><cites>FETCH-LOGICAL-c460t-5430d5374bce604701c8f1bf81ea30b3ec19826c30933791416e20061bbd6c423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpedsurg.2003.09.015$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,4022,27921,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15433525$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14694373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanaka, Shinji</creatorcontrib><creatorcontrib>Tajiri, Tatsuro</creatorcontrib><creatorcontrib>Noguchi, Shin-ichi</creatorcontrib><creatorcontrib>Shono, Kumiko</creatorcontrib><creatorcontrib>Ihara, Kenji</creatorcontrib><creatorcontrib>Hara, Toshiro</creatorcontrib><creatorcontrib>Suita, Sachiyo</creatorcontrib><title>Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>The amplification of the
MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of
MYCN remains controversial. To reassess the clinical implications of
MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the
MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses.
Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (
MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of
MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 23 samples were analyzed for
MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (
MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method.
Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 46 samples showed
MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of
MYCN-amplified cells. The cases of
MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of >1 year at diagnosis [
P < .0001], nonmass screening [
P = .0003], advanced stage [
P < .0001], diploid or tetraploid [
P < .0001], and a Shimada unfavorable histology [
P < .0001]).
MYCN gene dosages of more than 2.0 were significantly associated with a high expression of
MYCN (
P = .0459). However, the expression level of
MYCN was not significantly associated with any other prognostic factors.
Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the
MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of
MYCN amplification. In this highly sensitive analysis,
MYCN amplification (
MYCN/p53 ≥ 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of
MYCN does not appear to be an independently significant prognosis factor.</description><subject>Biological and medical sciences</subject><subject>Carbohydrates (enzymatic deficiencies). Glycogenosis</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>DNA - isolation & purification</subject><subject>Errors of metabolism</subject><subject>Female</subject><subject>FISH</subject><subject>Gene Amplification</subject><subject>Gene Dosage</subject><subject>Gene Expression</subject><subject>General aspects</subject><subject>Humans</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Infant</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>MYCN</subject><subject>N-Myc Proto-Oncogene Protein</subject><subject>Neuroblastoma</subject><subject>Neuroblastoma - genetics</subject><subject>Neuroblastoma - metabolism</subject><subject>Neurology</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Oncogene Proteins - genetics</subject><subject>Oncogene Proteins - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>quantitative polymerase chain reaction</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - genetics</subject><subject>RNA - isolation & purification</subject><subject>RNA - metabolism</subject><subject>Tumors of the nervous system. Phacomatoses</subject><issn>0022-3468</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2P0zAQhi0EYsvCX1j5AreEcZw4yQ1U8bHSAhc4cLIcZ5K6cp3iSSr673HUoj3uySP5mXfGjxm7E5ALEOr9Pt8fsacljnkBIHNocxDVM7YRlRRZBbJ-zjYARZHJUjU37BXRHhJYg3jJbkSp2lLWcsNOW--Cs8ZzcmNwQyqDRT4N3PCdG3f-zAkDudmdkJtg_Jkc8WGKfMSAvJ_IjOtFz-cdcvx7jEjkpsA9ntCvOd9-b79zF3jAJU6dNzRPB_OavRiMJ3xzPW_Zr8-ffm6_Zg8_vtxvPz5ktlQwZ1Upoa9kXXYWFZRpedsMohsagUZCJ9GKtimUldBKWbeiFAqTDiW6rle2LOQte3fJPcbpz4I064Mji96bgNNCugGoZS0ggeoC2jgRRRz0MbqDiWctQK_G9V7_N65X4xpanYynxrvrhKU7YP_YdlWcgLdXwFDyPMQk2NEjl94oq2IN-nDhMPk4OYyarMP0Gb2LaGfdT-6pXf4Bvc6i5g</recordid><startdate>2004</startdate><enddate>2004</enddate><creator>Tanaka, Shinji</creator><creator>Tajiri, Tatsuro</creator><creator>Noguchi, Shin-ichi</creator><creator>Shono, Kumiko</creator><creator>Ihara, Kenji</creator><creator>Hara, Toshiro</creator><creator>Suita, Sachiyo</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>2004</creationdate><title>Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma</title><author>Tanaka, Shinji ; Tajiri, Tatsuro ; Noguchi, Shin-ichi ; Shono, Kumiko ; Ihara, Kenji ; Hara, Toshiro ; Suita, Sachiyo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-5430d5374bce604701c8f1bf81ea30b3ec19826c30933791416e20061bbd6c423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Biological and medical sciences</topic><topic>Carbohydrates (enzymatic deficiencies). Glycogenosis</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>DNA - isolation & purification</topic><topic>Errors of metabolism</topic><topic>Female</topic><topic>FISH</topic><topic>Gene Amplification</topic><topic>Gene Dosage</topic><topic>Gene Expression</topic><topic>General aspects</topic><topic>Humans</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Infant</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>MYCN</topic><topic>N-Myc Proto-Oncogene Protein</topic><topic>Neuroblastoma</topic><topic>Neuroblastoma - genetics</topic><topic>Neuroblastoma - metabolism</topic><topic>Neurology</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Oncogene Proteins - genetics</topic><topic>Oncogene Proteins - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>quantitative polymerase chain reaction</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - genetics</topic><topic>RNA - isolation & purification</topic><topic>RNA - metabolism</topic><topic>Tumors of the nervous system. Phacomatoses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tanaka, Shinji</creatorcontrib><creatorcontrib>Tajiri, Tatsuro</creatorcontrib><creatorcontrib>Noguchi, Shin-ichi</creatorcontrib><creatorcontrib>Shono, Kumiko</creatorcontrib><creatorcontrib>Ihara, Kenji</creatorcontrib><creatorcontrib>Hara, Toshiro</creatorcontrib><creatorcontrib>Suita, Sachiyo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pediatric surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanaka, Shinji</au><au>Tajiri, Tatsuro</au><au>Noguchi, Shin-ichi</au><au>Shono, Kumiko</au><au>Ihara, Kenji</au><au>Hara, Toshiro</au><au>Suita, Sachiyo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2004</date><risdate>2004</risdate><volume>39</volume><issue>1</issue><spage>63</spage><epage>68</epage><pages>63-68</pages><issn>0022-3468</issn><eissn>1531-5037</eissn><coden>JPDSA3</coden><abstract>The amplification of the
MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of
MYCN remains controversial. To reassess the clinical implications of
MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the
MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses.
Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (
MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of
MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 23 samples were analyzed for
MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (
MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method.
Of the 54 samples with a single copy of
MYCN based on the Southern blotting method, 46 samples showed
MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of
MYCN-amplified cells. The cases of
MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of >1 year at diagnosis [
P < .0001], nonmass screening [
P = .0003], advanced stage [
P < .0001], diploid or tetraploid [
P < .0001], and a Shimada unfavorable histology [
P < .0001]).
MYCN gene dosages of more than 2.0 were significantly associated with a high expression of
MYCN (
P = .0459). However, the expression level of
MYCN was not significantly associated with any other prognostic factors.
Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the
MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of
MYCN amplification. In this highly sensitive analysis,
MYCN amplification (
MYCN/p53 ≥ 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of
MYCN does not appear to be an independently significant prognosis factor.</abstract><cop>Philadelphia, PA</cop><pub>Elsevier Inc</pub><pmid>14694373</pmid><doi>10.1016/j.jpedsurg.2003.09.015</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of pediatric surgery, 2004, Vol.39 (1), p.63-68 |
| issn | 0022-3468 1531-5037 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Biological and medical sciences Carbohydrates (enzymatic deficiencies). Glycogenosis Child Child, Preschool DNA - isolation & purification Errors of metabolism Female FISH Gene Amplification Gene Dosage Gene Expression General aspects Humans In Situ Hybridization, Fluorescence Infant Male Medical sciences Metabolic diseases MYCN N-Myc Proto-Oncogene Protein Neuroblastoma Neuroblastoma - genetics Neuroblastoma - metabolism Neurology Nuclear Proteins - genetics Nuclear Proteins - metabolism Oncogene Proteins - genetics Oncogene Proteins - metabolism Polymerase Chain Reaction Prognosis quantitative polymerase chain reaction Reverse Transcriptase Polymerase Chain Reaction RNA - genetics RNA - isolation & purification RNA - metabolism Tumors of the nervous system. Phacomatoses |
| title | Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma |
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