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Somatic p53 mutations in human breast carcinomas in an Icelandic population : a prognostic factor
Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conser...
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Published in: | Cancer research (Chicago, Ill.) Ill.), 1993-04, Vol.53 (7), p.1637-1641 |
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description | Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001). |
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E</creator><creatorcontrib>THORLACIUS, S ; BÖRRESEN, A.-L ; EYFJÖRD, J. E</creatorcontrib><description>Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001).</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 8453635</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Biological and medical sciences ; Breast Neoplasms - genetics ; Chromosomes, Human, Pair 17 ; Conserved Sequence ; DNA Mutational Analysis - methods ; Exons - genetics ; Female ; Gene Deletion ; Genes, p53 - genetics ; Gynecology. Andrology. Obstetrics ; Humans ; Iceland ; Mammary gland diseases ; Medical sciences ; Middle Aged ; Molecular Sequence Data ; Mutation - genetics ; Polymerase Chain Reaction ; Prognosis ; Sensitivity and Specificity ; Tumors</subject><ispartof>Cancer research (Chicago, Ill.), 1993-04, Vol.53 (7), p.1637-1641</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4687704$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8453635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>THORLACIUS, S</creatorcontrib><creatorcontrib>BÖRRESEN, A.-L</creatorcontrib><creatorcontrib>EYFJÖRD, J. E</creatorcontrib><title>Somatic p53 mutations in human breast carcinomas in an Icelandic population : a prognostic factor</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001).</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - genetics</subject><subject>Chromosomes, Human, Pair 17</subject><subject>Conserved Sequence</subject><subject>DNA Mutational Analysis - methods</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Genes, p53 - genetics</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Iceland</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>Sensitivity and Specificity</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><recordid>eNo9kE9LxDAQxYMo67r6EYQcxFsh3WSS1Jssui4seFDPZZqmbqVNatIe_PZm1-Jp_rzfPB5zRpY5cJ0pIeCcLBljOgOh1pfkKsavNELOYEEWWgCXHJYE33yPY2voAJz205h67yJtHT1MPTpaBYtxpAaDaV1CT1La74zt0NXHQz9M3emMPlCkQ_CfzsejZYNm9OGaXDTYRXsz1xX5eH5637xk-9ftbvO4zw5rqcesVqCgUEwK5AiKoZQFAlvnCLJQKq1MxWsm8wp0w7QsmE08A6iFkHlR8RW5__NNCb4nG8eyb2NKmWJaP8VSgeQ8ZyKBtzM4Vb2tyyG0PYafcv5J0u9mHaPBrgnoTBv_MSG1UsnmF3pfaZk</recordid><startdate>19930401</startdate><enddate>19930401</enddate><creator>THORLACIUS, S</creator><creator>BÖRRESEN, A.-L</creator><creator>EYFJÖRD, J. E</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19930401</creationdate><title>Somatic p53 mutations in human breast carcinomas in an Icelandic population : a prognostic factor</title><author>THORLACIUS, S ; BÖRRESEN, A.-L ; EYFJÖRD, J. E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h268t-d757597064a3a570a669a5021a56977a57cb3d061b58f08690e759055d44619b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - genetics</topic><topic>Chromosomes, Human, Pair 17</topic><topic>Conserved Sequence</topic><topic>DNA Mutational Analysis - methods</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>Gene Deletion</topic><topic>Genes, p53 - genetics</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Iceland</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>Sensitivity and Specificity</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>THORLACIUS, S</creatorcontrib><creatorcontrib>BÖRRESEN, A.-L</creatorcontrib><creatorcontrib>EYFJÖRD, J. E</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>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>THORLACIUS, S</au><au>BÖRRESEN, A.-L</au><au>EYFJÖRD, J. E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic p53 mutations in human breast carcinomas in an Icelandic population : a prognostic factor</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>1993-04-01</date><risdate>1993</risdate><volume>53</volume><issue>7</issue><spage>1637</spage><epage>1641</epage><pages>1637-1641</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Mutations in the p53 gene are among the most common genetic changes in human carcinomas. They have been found in many tumor types including colon, lung, and breast. We have used constant denaturant gel electrophoresis in order to screen samples from 109 breast carcinomas for mutations in four conserved regions, exons 5, 7, and 8, of the p53 gene. Samples were also analyzed for allelic loss of the p53 gene and of markers more distal on chromosome 17 p. Mutations were confirmed by DNA sequencing. Mutations were found in 18 of the 109 samples (16.5%). Loss of heterozygosity at 17p was detected in the majority of informative mutated cases. All cases were also screened for germ line mutations, but none were found. The results obtained were analyzed with respect to clinical parameters and prognosis. There was a significant association between p53 mutation and low content of estrogen receptor protein in the tumors (P = 0.01). An association with poor prognosis was strongly indicated by mortality rates that were 37.5% among the patients with p53 mutation and 9.4% for the control group (mean follow up, 32 months). P53 mutation was found to be the strongest negative factor against survival in a covariate survival analysis (P = 0.001).</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>8453635</pmid><tpages>5</tpages></addata></record> |
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subjects | Adult Aged Aged, 80 and over Base Sequence Biological and medical sciences Breast Neoplasms - genetics Chromosomes, Human, Pair 17 Conserved Sequence DNA Mutational Analysis - methods Exons - genetics Female Gene Deletion Genes, p53 - genetics Gynecology. Andrology. Obstetrics Humans Iceland Mammary gland diseases Medical sciences Middle Aged Molecular Sequence Data Mutation - genetics Polymerase Chain Reaction Prognosis Sensitivity and Specificity Tumors |
title | Somatic p53 mutations in human breast carcinomas in an Icelandic population : a prognostic factor |
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