Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment
Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these...
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| Veröffentlicht in: | British journal of cancer 2008-06, Vol.98 (11), p.1845-1851 |
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| container_title | British journal of cancer |
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| creator | Badie, C Dziwura, S Raffy, C Tsigani, T Alsbeih, G Moody, J Finnon, P Levine, E Scott, D Bouffler, S |
| description | Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (
CDKN1A
,
GADD45A
,
CCNB1
, and
BBC3
) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of
BBC3
,
CCNB1
, and
GADD45A
2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for
CDKN1A
(
P |
| doi_str_mv | 10.1038/sj.bjc.6604381 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2410125</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1486319331</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-fb21a286c93b093b494bc53617e0ad6566ed19b54f7e655a71dad2682d18e5993</originalsourceid><addsrcrecordid>eNp1kb1PwzAQxS0EoqWwMqKIPak_YidZkKryKSpYYLacxGkdtXHxuUX97zFqRGFgsKzT_e690z2ELglOCGb5GNqkbKtECJyynByhIeGMxiSn2TEaYoyzGBcUD9AZQBvKAufZKRqQPC0YZekQ1ZNSO6c6H01vn1_IJPKhgMqZtTe2U8vIaVjbDnSkAGxllNcQfRq_iFTZWbcKBOgOjDdb43eRt5FTdaDCcJDSyq9058_RSaOWoC_6f4Te7-_epo_x7PXhaTqZxVXKuY-bkhJFc1EVrMThpUVaVpwJkmmsasGF0DUpSp42mRacq4zUqqYipzXJNS8KNkI3e931plzpugrWTi3l2pmVcjtplZF_O51ZyLndSpoSTCgPAte9gLMfGw1etnbjwhlAUoYxycJhA5TsocpZAKebHwOC5XcoEloZQpF9KGHg6vdaB7xPIQDjPQCh1c21O9j-I_kFTIKbKw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>230017182</pqid></control><display><type>article</type><title>Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment</title><source>MEDLINE</source><source>Springer Journals</source><source>Nature Journals Online</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Badie, C ; Dziwura, S ; Raffy, C ; Tsigani, T ; Alsbeih, G ; Moody, J ; Finnon, P ; Levine, E ; Scott, D ; Bouffler, S</creator><creatorcontrib>Badie, C ; Dziwura, S ; Raffy, C ; Tsigani, T ; Alsbeih, G ; Moody, J ; Finnon, P ; Levine, E ; Scott, D ; Bouffler, S</creatorcontrib><description>Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (
CDKN1A
,
GADD45A
,
CCNB1
, and
BBC3
) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of
BBC3
,
CCNB1
, and
GADD45A
2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for
CDKN1A
(
P
<0.002) in severe reactors compared to normal. Prediction of reaction severity of ∼91% of individuals sampled was achieved using this end point. Analysis of
TP53
Arg72Pro and
CDKN1A
Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6604381</identifier><identifier>PMID: 18493234</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adult ; Aged ; Apoptosis Regulatory Proteins - genetics ; Ataxia ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - radiotherapy ; Cancer Research ; Cancer therapies ; Cyclin B - genetics ; Cyclin B1 ; Cyclin-Dependent Kinase Inhibitor p21 - genetics ; Drug Resistance ; Epidemiology ; Female ; Gene expression ; Genes, p53 ; Humans ; Lymphocytes ; Medical research ; Middle Aged ; Molecular Diagnostics ; Molecular Medicine ; Oncology ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins - genetics ; Radiation therapy ; Radiation Tolerance ; Skin ; Toxicity ; Transcription, Genetic</subject><ispartof>British journal of cancer, 2008-06, Vol.98 (11), p.1845-1851</ispartof><rights>The Author(s) 2008</rights><rights>Copyright Nature Publishing Group Jun 3, 2008</rights><rights>Copyright © 2008 Cancer Research UK 2008 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-fb21a286c93b093b494bc53617e0ad6566ed19b54f7e655a71dad2682d18e5993</citedby><cites>FETCH-LOGICAL-c455t-fb21a286c93b093b494bc53617e0ad6566ed19b54f7e655a71dad2682d18e5993</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410125/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410125/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18493234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Badie, C</creatorcontrib><creatorcontrib>Dziwura, S</creatorcontrib><creatorcontrib>Raffy, C</creatorcontrib><creatorcontrib>Tsigani, T</creatorcontrib><creatorcontrib>Alsbeih, G</creatorcontrib><creatorcontrib>Moody, J</creatorcontrib><creatorcontrib>Finnon, P</creatorcontrib><creatorcontrib>Levine, E</creatorcontrib><creatorcontrib>Scott, D</creatorcontrib><creatorcontrib>Bouffler, S</creatorcontrib><title>Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (
CDKN1A
,
GADD45A
,
CCNB1
, and
BBC3
) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of
BBC3
,
CCNB1
, and
GADD45A
2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for
CDKN1A
(
P
<0.002) in severe reactors compared to normal. Prediction of reaction severity of ∼91% of individuals sampled was achieved using this end point. Analysis of
TP53
Arg72Pro and
CDKN1A
Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.</description><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Ataxia</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - radiotherapy</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Cyclin B - genetics</subject><subject>Cyclin B1</subject><subject>Cyclin-Dependent Kinase Inhibitor p21 - genetics</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes, p53</subject><subject>Humans</subject><subject>Lymphocytes</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Radiation therapy</subject><subject>Radiation Tolerance</subject><subject>Skin</subject><subject>Toxicity</subject><subject>Transcription, Genetic</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kb1PwzAQxS0EoqWwMqKIPak_YidZkKryKSpYYLacxGkdtXHxuUX97zFqRGFgsKzT_e690z2ELglOCGb5GNqkbKtECJyynByhIeGMxiSn2TEaYoyzGBcUD9AZQBvKAufZKRqQPC0YZekQ1ZNSO6c6H01vn1_IJPKhgMqZtTe2U8vIaVjbDnSkAGxllNcQfRq_iFTZWbcKBOgOjDdb43eRt5FTdaDCcJDSyq9058_RSaOWoC_6f4Te7-_epo_x7PXhaTqZxVXKuY-bkhJFc1EVrMThpUVaVpwJkmmsasGF0DUpSp42mRacq4zUqqYipzXJNS8KNkI3e931plzpugrWTi3l2pmVcjtplZF_O51ZyLndSpoSTCgPAte9gLMfGw1etnbjwhlAUoYxycJhA5TsocpZAKebHwOC5XcoEloZQpF9KGHg6vdaB7xPIQDjPQCh1c21O9j-I_kFTIKbKw</recordid><startdate>20080603</startdate><enddate>20080603</enddate><creator>Badie, C</creator><creator>Dziwura, S</creator><creator>Raffy, C</creator><creator>Tsigani, T</creator><creator>Alsbeih, G</creator><creator>Moody, J</creator><creator>Finnon, P</creator><creator>Levine, E</creator><creator>Scott, D</creator><creator>Bouffler, S</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</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>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20080603</creationdate><title>Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment</title><author>Badie, C ; Dziwura, S ; Raffy, C ; Tsigani, T ; Alsbeih, G ; Moody, J ; Finnon, P ; Levine, E ; Scott, D ; Bouffler, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-fb21a286c93b093b494bc53617e0ad6566ed19b54f7e655a71dad2682d18e5993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Ataxia</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - radiotherapy</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Cyclin B - genetics</topic><topic>Cyclin B1</topic><topic>Cyclin-Dependent Kinase Inhibitor p21 - genetics</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes, p53</topic><topic>Humans</topic><topic>Lymphocytes</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Radiation therapy</topic><topic>Radiation Tolerance</topic><topic>Skin</topic><topic>Toxicity</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Badie, C</creatorcontrib><creatorcontrib>Dziwura, S</creatorcontrib><creatorcontrib>Raffy, C</creatorcontrib><creatorcontrib>Tsigani, T</creatorcontrib><creatorcontrib>Alsbeih, G</creatorcontrib><creatorcontrib>Moody, J</creatorcontrib><creatorcontrib>Finnon, P</creatorcontrib><creatorcontrib>Levine, E</creatorcontrib><creatorcontrib>Scott, 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S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2008-06-03</date><risdate>2008</risdate><volume>98</volume><issue>11</issue><spage>1845</spage><epage>1851</epage><pages>1845-1851</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (
CDKN1A
,
GADD45A
,
CCNB1
, and
BBC3
) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of
BBC3
,
CCNB1
, and
GADD45A
2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for
CDKN1A
(
P
<0.002) in severe reactors compared to normal. Prediction of reaction severity of ∼91% of individuals sampled was achieved using this end point. Analysis of
TP53
Arg72Pro and
CDKN1A
Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18493234</pmid><doi>10.1038/sj.bjc.6604381</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Journals; Nature Journals Online; PubMed Central; EZB Electronic Journals Library |
| subjects | Adult Aged Apoptosis Regulatory Proteins - genetics Ataxia Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - genetics Breast Neoplasms - radiotherapy Cancer Research Cancer therapies Cyclin B - genetics Cyclin B1 Cyclin-Dependent Kinase Inhibitor p21 - genetics Drug Resistance Epidemiology Female Gene expression Genes, p53 Humans Lymphocytes Medical research Middle Aged Molecular Diagnostics Molecular Medicine Oncology Polymorphism, Single Nucleotide Proto-Oncogene Proteins - genetics Radiation therapy Radiation Tolerance Skin Toxicity Transcription, Genetic |
| title | Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment |
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