A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma: Lymphoma
The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to d...
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| Veröffentlicht in: | Leukemia 2005-08, Vol.19 (8), p.1459-1465 |
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| creator | Davies, A J Lee, A M Taylor, C Clear, A J Goff, L K Iqbal, S Cuthbert-Heavens, D Calaminici, M Norton, A J Lister, T A Fitzgibbon, J |
| description | The role of
TP53
mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire
TP53
coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated
TP53
arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the
TP53
locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with
wtTP53
. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68–76%) than FL (mean 58% positive; 95% CI 54–62%) (
P |
| doi_str_mv | 10.1038/sj.leu.2403802 |
| format | Article |
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TP53
mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire
TP53
coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated
TP53
arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the
TP53
locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with
wtTP53
. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68–76%) than FL (mean 58% positive; 95% CI 54–62%) (
P
<0.001) but did not correlate with
TP53
status.
TP53
mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2403802</identifier><identifier>PMID: 15902285</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>B-cell lymphoma ; Biopsy ; Cancer ; Cancer Research ; Cell cycle ; Cell Transformation, Neoplastic - genetics ; Confidence intervals ; Critical Care Medicine ; Dentistry ; Gene Expression Regulation, Neoplastic ; Genetic transformation ; Hematology ; Heterozygosity ; Hospitals ; Humans ; Immunocytochemistry ; Immunohistochemistry ; Intensive ; Internal Medicine ; Leukemia ; Loss of Heterozygosity ; Lymph nodes ; Lymph Nodes - pathology ; Lymphatic system ; Lymphocytes B ; Lymphoma ; Lymphoma, B-Cell - pathology ; Lymphoma, Follicular - pathology ; Lymphoma, Large B-Cell, Diffuse - pathology ; MDM2 protein ; Medical prognosis ; Medical research ; Medicine ; Medicine & Public Health ; Missense mutation ; Mutation ; Mutation, Missense ; Neoplasm Proteins - analysis ; Nuclear Proteins - analysis ; Oncology ; original-manuscript ; Patients ; Proteins ; Proto-Oncogene Proteins - analysis ; Proto-Oncogene Proteins c-mdm2 ; Therapeutic targets ; Transformations ; Tumor Suppressor Protein p53 - analysis ; Tumor Suppressor Protein p53 - genetics</subject><ispartof>Leukemia, 2005-08, Vol.19 (8), p.1459-1465</ispartof><rights>Springer Nature Limited 2005</rights><rights>Leukemia (2005) 19, 1459-1465.</rights><rights>COPYRIGHT 2005 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2005</rights><rights>Nature Publishing Group 2005.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c623t-7f322b04f2ad63ab95e6f010565a0222dfb84bb22ffe128de783a1aa4c631cc23</citedby><cites>FETCH-LOGICAL-c623t-7f322b04f2ad63ab95e6f010565a0222dfb84bb22ffe128de783a1aa4c631cc23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15902285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Davies, A J</creatorcontrib><creatorcontrib>Lee, A M</creatorcontrib><creatorcontrib>Taylor, C</creatorcontrib><creatorcontrib>Clear, A J</creatorcontrib><creatorcontrib>Goff, L K</creatorcontrib><creatorcontrib>Iqbal, S</creatorcontrib><creatorcontrib>Cuthbert-Heavens, D</creatorcontrib><creatorcontrib>Calaminici, M</creatorcontrib><creatorcontrib>Norton, A J</creatorcontrib><creatorcontrib>Lister, T A</creatorcontrib><creatorcontrib>Fitzgibbon, J</creatorcontrib><title>A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma: Lymphoma</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>The role of
TP53
mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire
TP53
coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated
TP53
arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the
TP53
locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with
wtTP53
. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68–76%) than FL (mean 58% positive; 95% CI 54–62%) (
P
<0.001) but did not correlate with
TP53
status.
TP53
mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target.</description><subject>B-cell lymphoma</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell cycle</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Confidence intervals</subject><subject>Critical Care Medicine</subject><subject>Dentistry</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic transformation</subject><subject>Hematology</subject><subject>Heterozygosity</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunocytochemistry</subject><subject>Immunohistochemistry</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Loss of Heterozygosity</subject><subject>Lymph nodes</subject><subject>Lymph Nodes - pathology</subject><subject>Lymphatic system</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Lymphoma, B-Cell - pathology</subject><subject>Lymphoma, Follicular - pathology</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>MDM2 protein</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Missense mutation</subject><subject>Mutation</subject><subject>Mutation, Missense</subject><subject>Neoplasm Proteins - analysis</subject><subject>Nuclear Proteins - analysis</subject><subject>Oncology</subject><subject>original-manuscript</subject><subject>Patients</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins - analysis</subject><subject>Proto-Oncogene Proteins c-mdm2</subject><subject>Therapeutic targets</subject><subject>Transformations</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkk1v3CAQhlHVqtmmvfZYoVbKzRvAgPFxE_VLitQe0jPC9rDLCswW7EP-fbF21W2rRBUHxMwzLzPwIvSWkjUltbrO-7WHec14ORD2DK0ob2QlhKDP0Yoo1VSyZfwCvcp5T8iSlC_RBRUtYUyJFRo32LvgJhhwih6wjQnffxc1DvNkJhdH7EY87QBPyYy5ZMMxGm1BvXf97E3C_iEcdjEYPEU8OGvnDLjEt4Bvqh68_w28Ri-s8RnenPZL9OPTx_vbL9Xdt89fbzd3VS9ZPVWNrRnrCLfMDLI2XStAWkKJkMKUxtlgO8W7jjFrgTI1QKNqQ43hvaxp37P6El0ddQ8p_pwhTzq4vHRiRohz1lIRSWre_BekbSsIl7yAH_4B93FOYxlCM8lFQ0TLZKHeP0kxIhpOWnWW2hoP2o02lsftl3v1hiolGG_VQq0focoaILg-jmBdif9VcPVHwQ6Mn3Y5-nn5r_yocp9izgmsPiQXTHrQlOjFVTrvdXGVPrmqFLw7TTV3AYYzfrJRAa6PQC6pcQvpPPYTkr8AsejVfg</recordid><startdate>20050801</startdate><enddate>20050801</enddate><creator>Davies, A J</creator><creator>Lee, A M</creator><creator>Taylor, C</creator><creator>Clear, A J</creator><creator>Goff, L K</creator><creator>Iqbal, S</creator><creator>Cuthbert-Heavens, D</creator><creator>Calaminici, M</creator><creator>Norton, A J</creator><creator>Lister, T A</creator><creator>Fitzgibbon, J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20050801</creationdate><title>A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma</title><author>Davies, A J ; Lee, A M ; Taylor, C ; Clear, A J ; Goff, L K ; Iqbal, S ; Cuthbert-Heavens, D ; Calaminici, M ; Norton, A J ; Lister, T A ; Fitzgibbon, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c623t-7f322b04f2ad63ab95e6f010565a0222dfb84bb22ffe128de783a1aa4c631cc23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>B-cell lymphoma</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cell cycle</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Confidence intervals</topic><topic>Critical Care Medicine</topic><topic>Dentistry</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic transformation</topic><topic>Hematology</topic><topic>Heterozygosity</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunocytochemistry</topic><topic>Immunohistochemistry</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Loss of Heterozygosity</topic><topic>Lymph nodes</topic><topic>Lymph Nodes - pathology</topic><topic>Lymphatic system</topic><topic>Lymphocytes B</topic><topic>Lymphoma</topic><topic>Lymphoma, B-Cell - pathology</topic><topic>Lymphoma, Follicular - pathology</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>MDM2 protein</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Missense mutation</topic><topic>Mutation</topic><topic>Mutation, Missense</topic><topic>Neoplasm Proteins - analysis</topic><topic>Nuclear Proteins - analysis</topic><topic>Oncology</topic><topic>original-manuscript</topic><topic>Patients</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins - analysis</topic><topic>Proto-Oncogene Proteins c-mdm2</topic><topic>Therapeutic targets</topic><topic>Transformations</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Davies, A J</creatorcontrib><creatorcontrib>Lee, A M</creatorcontrib><creatorcontrib>Taylor, C</creatorcontrib><creatorcontrib>Clear, A J</creatorcontrib><creatorcontrib>Goff, L K</creatorcontrib><creatorcontrib>Iqbal, S</creatorcontrib><creatorcontrib>Cuthbert-Heavens, D</creatorcontrib><creatorcontrib>Calaminici, M</creatorcontrib><creatorcontrib>Norton, A J</creatorcontrib><creatorcontrib>Lister, T A</creatorcontrib><creatorcontrib>Fitzgibbon, J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Davies, A J</au><au>Lee, A M</au><au>Taylor, C</au><au>Clear, A J</au><au>Goff, L K</au><au>Iqbal, S</au><au>Cuthbert-Heavens, D</au><au>Calaminici, M</au><au>Norton, A J</au><au>Lister, T A</au><au>Fitzgibbon, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma: Lymphoma</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2005-08-01</date><risdate>2005</risdate><volume>19</volume><issue>8</issue><spage>1459</spage><epage>1465</epage><pages>1459-1465</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>The role of
TP53
mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire
TP53
coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated
TP53
arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the
TP53
locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with
wtTP53
. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68–76%) than FL (mean 58% positive; 95% CI 54–62%) (
P
<0.001) but did not correlate with
TP53
status.
TP53
mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15902285</pmid><doi>10.1038/sj.leu.2403802</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Leukemia, 2005-08, Vol.19 (8), p.1459-1465 |
| issn | 0887-6924 1476-5551 |
| language | eng |
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| source | MEDLINE; Nature; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | B-cell lymphoma Biopsy Cancer Cancer Research Cell cycle Cell Transformation, Neoplastic - genetics Confidence intervals Critical Care Medicine Dentistry Gene Expression Regulation, Neoplastic Genetic transformation Hematology Heterozygosity Hospitals Humans Immunocytochemistry Immunohistochemistry Intensive Internal Medicine Leukemia Loss of Heterozygosity Lymph nodes Lymph Nodes - pathology Lymphatic system Lymphocytes B Lymphoma Lymphoma, B-Cell - pathology Lymphoma, Follicular - pathology Lymphoma, Large B-Cell, Diffuse - pathology MDM2 protein Medical prognosis Medical research Medicine Medicine & Public Health Missense mutation Mutation Mutation, Missense Neoplasm Proteins - analysis Nuclear Proteins - analysis Oncology original-manuscript Patients Proteins Proto-Oncogene Proteins - analysis Proto-Oncogene Proteins c-mdm2 Therapeutic targets Transformations Tumor Suppressor Protein p53 - analysis Tumor Suppressor Protein p53 - genetics |
| title | A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma: Lymphoma |
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