Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years
Identifieur interne : 009E19 ( Main/Exploration ); précédent : 009E18; suivant : 009E20Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years
Auteurs : Kathryn Alsop [Australie] ; Leeanne Mead [Australie] ; Letitia D. Smith [Australie] ; Simon G. Royce [Australie] ; Andrea A. Tesoriero [Australie] ; Joanne P. Young [Australie] ; Andrew Haydon [Australie] ; Carry Grubb [Australie] ; Graham G. Giles [Australie] ; Mark A. Jenkins [Australie] ; John L. Hopper [Australie] ; Melissa C. Southey [Australie, France]Source :
- European journal of cancer : (1990) [ 0959-8049 ] ; 2006.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Pharmacologie.
English descriptors
- KwdEn :
Abstract
Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. In this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G > T transitions and 1 G> A) and one in codon 13 (G > A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2. The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal cancer of later age of onset.
Affiliations:
- Australie, France
- Auvergne-Rhône-Alpes, Rhône-Alpes, Victoria (État)
- Lyon, Melbourne
- Université de Melbourne
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Smith</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne</s1><s2>Vic</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Royce, Simon G" sort="Royce, Simon G" uniqKey="Royce S" first="Simon G." last="Royce">Simon G. Royce</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne</s1><s2>Vic</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Tesoriero, Andrea A" sort="Tesoriero, Andrea A" uniqKey="Tesoriero A" first="Andrea A." last="Tesoriero">Andrea A. Tesoriero</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne</s1><s2>Vic</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Young, Joanne P" sort="Young, Joanne P" uniqKey="Young J" first="Joanne P." last="Young">Joanne P. Young</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research</s1><s2>Qld</s2><s3>AUS</s3><sZ>6 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Qld</wicri:noRegion></affiliation></author><author><name sortKey="Haydon, Andrew" sort="Haydon, Andrew" uniqKey="Haydon A" first="Andrew" last="Haydon">Andrew Haydon</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Epidemiology and Preventative Medicine, Monash University</s1><s3>AUS</s3><sZ>7 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Department of Epidemiology and Preventative Medicine, Monash University</wicri:noRegion></affiliation></author><author><name sortKey="Grubb, Carry" sort="Grubb, Carry" uniqKey="Grubb C" first="Carry" last="Grubb">Carry Grubb</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Anatomical Pathology, Western Hospital</s1><s2>Vic</s2><s3>AUS</s3><sZ>8 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Vic</wicri:noRegion></affiliation></author><author><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Centre for Cancer Epidemiology, The Cancer Council Victoria</s1><s3>AUS</s3><sZ>9 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Centre for Cancer Epidemiology, The Cancer Council Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Vic</s2><s3>AUS</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne</s1><s2>Vic</s2><s3>AUS</s3><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne</s1><s2>Vic</s2><s3>AUS</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="07"><s1>International Agency for Research on Cancer</s1><s2>Lyon</s2><s3>FRA</s3><sZ>12 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">European journal of cancer : (1990)</title><title level="j" type="abbreviated">Eur. j. cancer : (1990)</title><idno type="ISSN">0959-8049</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">European journal of cancer : (1990)</title><title level="j" type="abbreviated">Eur. j. cancer : (1990)</title><idno type="ISSN">0959-8049</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age of onset</term><term>C-Onc gene</term><term>Cancerology</term><term>Colorectal cancer</term><term>Diagnosis</term><term>Early</term><term>K ras Gene</term><term>Low frequency</term><term>Onc gene</term><term>Pharmacology</term><term>Protooncogene</term><term>Ras gene</term><term>Somatic mutation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Cancer colorectal</term><term>Basse fréquence</term><term>Mutation somatique</term><term>Gène onc</term><term>Gène K ras</term><term>Gène onc cellulaire</term><term>Protooncogène</term><term>Gène ras</term><term>Diagnostic</term><term>Age apparition</term><term>Précoce</term><term>Cancérologie</term><term>Pharmacologie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Pharmacologie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. In this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G > T transitions and 1 G> A) and one in codon 13 (G > A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2. The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal cancer of later age of onset.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li><li>Victoria (État)</li></region><settlement><li>Lyon</li><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><region name="Victoria (État)"><name sortKey="Alsop, Kathryn" sort="Alsop, Kathryn" uniqKey="Alsop K" first="Kathryn" last="Alsop">Kathryn Alsop</name></region><name sortKey="Giles, Graham G" sort="Giles, Graham G" uniqKey="Giles G" first="Graham G." last="Giles">Graham G. Giles</name><name sortKey="Grubb, Carry" sort="Grubb, Carry" uniqKey="Grubb C" first="Carry" last="Grubb">Carry Grubb</name><name sortKey="Haydon, Andrew" sort="Haydon, Andrew" uniqKey="Haydon A" first="Andrew" last="Haydon">Andrew Haydon</name><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name><name sortKey="Jenkins, Mark A" sort="Jenkins, Mark A" uniqKey="Jenkins M" first="Mark A." last="Jenkins">Mark A. Jenkins</name><name sortKey="Mead, Leeanne" sort="Mead, Leeanne" uniqKey="Mead L" first="Leeanne" last="Mead">Leeanne Mead</name><name sortKey="Royce, Simon G" sort="Royce, Simon G" uniqKey="Royce S" first="Simon G." last="Royce">Simon G. Royce</name><name sortKey="Smith, Letitia D" sort="Smith, Letitia D" uniqKey="Smith L" first="Letitia D." last="Smith">Letitia D. Smith</name><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name><name sortKey="Tesoriero, Andrea A" sort="Tesoriero, Andrea A" uniqKey="Tesoriero A" first="Andrea A." last="Tesoriero">Andrea A. Tesoriero</name><name sortKey="Young, Joanne P" sort="Young, Joanne P" uniqKey="Young J" first="Joanne P." last="Young">Joanne P. Young</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Southey, Melissa C" sort="Southey, Melissa C" uniqKey="Southey M" first="Melissa C." last="Southey">Melissa C. Southey</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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