PittsburghV1, Main, Exploration, bibRecord, 002010

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Identifieur interne : 002010 ( Main/Exploration ); précédent : 002009; suivant : 002011

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Auteurs : Andrew M. Gross [États-Unis] ; Ryan K. Orosco [États-Unis] ; John P. Shen [États-Unis] ; Ann Marie Egloff [États-Unis] ; Hannah Carter [États-Unis] ; Matan Hofree [États-Unis] ; Michel Choueiri [États-Unis] ; Charles S. Coffey [États-Unis] ; Scott M. Lippman [États-Unis] ; D. Neil Hayes [États-Unis] ; Ezra E. Cohen [États-Unis] ; Jennifer R. Grandis [États-Unis] ; Quyen T. Nguyen [États-Unis] ; Trey Ideker [États-Unis]

Source :

Nature genetics [ 1061-4036 ] ; 2014.

RBID : PMC:4146706

Descripteurs français

English descriptors

KwdEn :
- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell (genetics), Carcinoma, Squamous Cell (pathology), Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 3, Genes, p53, Genomics (methods), Head and Neck Neoplasms (genetics), Head and Neck Neoplasms (pathology), Humans, Infant, Infant, Newborn, Middle Aged, Mutation, Prognosis, Tumor Suppressor Protein p53 (genetics), Young Adult.
MESH :
- chemical , genetics : Tumor Suppressor Protein p53.
- genetics : Carcinoma, Squamous Cell, Head and Neck Neoplasms.
- methods : Genomics.
- pathology : Carcinoma, Squamous Cell, Head and Neck Neoplasms.
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 3, Genes, p53, Humans, Infant, Infant, Newborn, Middle Aged, Mutation, Prognosis, Young Adult.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p, and that the combination of both events associates with a surprising decrease in survival rates (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p, rather than a consequence of global genome instability, and validates in HNSCC and pan-cancer cohorts. In Human Papilloma Virus positive (HPV+) tumors, in which HPV inactivates TP53, 3p deletion is also common and associates with poor outcomes. The TP53-3p event is modified by mir-548k expression which decreases survival even further, while it is mutually exclusive with mutations to RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146706

DOI: 10.1038/ng.3051
PubMed: 25086664
PubMed Central: 4146706

Affiliations:

Le document en format XML

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 mutation to 3p loss</title>
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 mutation to 3p loss</title>
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<author><name sortKey="Grandis, Jennifer R" sort="Grandis, Jennifer R" uniqKey="Grandis J" first="Jennifer R" last="Grandis">Jennifer R. Grandis</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
</author>
<author><name sortKey="Nguyen, Quyen T" sort="Nguyen, Quyen T" uniqKey="Nguyen Q" first="Quyen T" last="Nguyen">Quyen T. Nguyen</name>
<affiliation wicri:level="2"><nlm:aff id="A2">Division of Head and Neck Surgery, University of California San Diego, La Jolla, CA 92093, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Head and Neck Surgery, University of California San Diego, La Jolla, CA 92093</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A6">Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ideker, Trey" sort="Ideker, Trey" uniqKey="Ideker T" first="Trey" last="Ideker">Trey Ideker</name>
<affiliation wicri:level="2"><nlm:aff id="A1">Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Bioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA 92093</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A3">Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine, University of California, San Diego, La Jolla, CA 92093</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A5">Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A6">Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature genetics</title>
<idno type="ISSN">1061-4036</idno>
<idno type="eISSN">1546-1718</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Carcinoma, Squamous Cell (genetics)</term>
<term>Carcinoma, Squamous Cell (pathology)</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Chromosome Deletion</term>
<term>Chromosomes, Human, Pair 3</term>
<term>Genes, p53</term>
<term>Genomics (methods)</term>
<term>Head and Neck Neoplasms (genetics)</term>
<term>Head and Neck Neoplasms (pathology)</term>
<term>Humans</term>
<term>Infant</term>
<term>Infant, Newborn</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Prognosis</term>
<term>Tumor Suppressor Protein p53 (genetics)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Carcinome épidermoïde (anatomopathologie)</term>
<term>Carcinome épidermoïde (génétique)</term>
<term>Chromosomes humains de la paire 3</term>
<term>Délétion de segment de chromosome</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Gènes p53</term>
<term>Génomique ()</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mutation</term>
<term>Nourrisson</term>
<term>Nouveau-né</term>
<term>Pronostic</term>
<term>Protéine p53 suppresseur de tumeur (génétique)</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>Tumeurs de la tête et du cou (anatomopathologie)</term>
<term>Tumeurs de la tête et du cou (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Tumor Suppressor Protein p53</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome épidermoïde</term>
<term>Tumeurs de la tête et du cou</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Carcinome épidermoïde</term>
<term>Protéine p53 suppresseur de tumeur</term>
<term>Tumeurs de la tête et du cou</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genomics</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Carcinoma, Squamous Cell</term>
<term>Head and Neck Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Chromosome Deletion</term>
<term>Chromosomes, Human, Pair 3</term>
<term>Genes, p53</term>
<term>Humans</term>
<term>Infant</term>
<term>Infant, Newborn</term>
<term>Middle Aged</term>
<term>Mutation</term>
<term>Prognosis</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Chromosomes humains de la paire 3</term>
<term>Délétion de segment de chromosome</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Gènes p53</term>
<term>Génomique</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mutation</term>
<term>Nourrisson</term>
<term>Nouveau-né</term>
<term>Pronostic</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P1">Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that <italic>TP53</italic>
 mutation is frequently accompanied by loss of chromosome 3p, and that the combination of both events associates with a surprising decrease in survival rates (1.9 years versus >5 years for <italic>TP53</italic>
 mutation alone). The <italic>TP53</italic>
-3p interaction is specific to chromosome 3p, rather than a consequence of global genome instability, and validates in HNSCC and pan-cancer cohorts. In Human Papilloma Virus positive (HPV+) tumors, in which HPV inactivates <italic>TP53</italic>
, 3p deletion is also common and associates with poor outcomes. The <italic>TP53</italic>
-3p event is modified by mir-548k expression which decreases survival even further, while it is mutually exclusive with mutations to RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Leemans, Cr" uniqKey="Leemans C">CR Leemans</name>
</author>
<author><name sortKey="Braakhuis, Bjm" uniqKey="Braakhuis B">BJM Braakhuis</name>
</author>
<author><name sortKey="Brakenhoff, Rh" uniqKey="Brakenhoff R">RH Brakenhoff</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mroz, Ea" uniqKey="Mroz E">EA Mroz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stransky, N" uniqKey="Stransky N">N Stransky</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chung, Ch" uniqKey="Chung C">CH Chung</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walter, V" uniqKey="Walter V">V Walter</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pickering, Cr" uniqKey="Pickering C">CR Pickering</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Temam, S" uniqKey="Temam S">S Temam</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lui, Vwy" uniqKey="Lui V">VWY Lui</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Perez, F" uniqKey="Perez F">F Perez</name>
</author>
<author><name sortKey="Granger, Be" uniqKey="Granger B">BE Granger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Poeta, Ml" uniqKey="Poeta M">ML Poeta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ohta, M" uniqKey="Ohta M">M Ohta</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rosin, Mp" uniqKey="Rosin M">MP Rosin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Partridge, M" uniqKey="Partridge M">M Partridge</name>
</author>
<author><name sortKey="Emilion, G" uniqKey="Emilion G">G Emilion</name>
</author>
<author><name sortKey="Langdon, Jd" uniqKey="Langdon J">JD Langdon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meredith, Sd" uniqKey="Meredith S">SD Meredith</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Partridge, M" uniqKey="Partridge M">M Partridge</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ciriello, G" uniqKey="Ciriello G">G Ciriello</name>
</author>
<author><name sortKey="Cerami, E" uniqKey="Cerami E">E Cerami</name>
</author>
<author><name sortKey="Sander, C" uniqKey="Sander C">C Sander</name>
</author>
<author><name sortKey="Schultz, N" uniqKey="Schultz N">N Schultz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bredel, M" uniqKey="Bredel M">M Bredel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thomas, M" uniqKey="Thomas M">M Thomas</name>
</author>
<author><name sortKey="Pim, D" uniqKey="Pim D">D Pim</name>
</author>
<author><name sortKey="Banks, L" uniqKey="Banks L">L Banks</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Marur, S" uniqKey="Marur S">S Marur</name>
</author>
<author><name sortKey="D Souza, G" uniqKey="D Souza G">G D'Souza</name>
</author>
<author><name sortKey="Westra, Wh" uniqKey="Westra W">WH Westra</name>
</author>
<author><name sortKey="Forastiere, Aa" uniqKey="Forastiere A">AA Forastiere</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chang, K" uniqKey="Chang K">K Chang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Song, Y" uniqKey="Song Y">Y Song</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lawrence, Ms" uniqKey="Lawrence M">MS Lawrence</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Xing, F" uniqKey="Xing F">F Xing</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A McKenna</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liberzon, A" uniqKey="Liberzon A">A Liberzon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mermel, Ch" uniqKey="Mermel C">CH Mermel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mell, Lk" uniqKey="Mell L">LK Mell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Farshadpour, F" uniqKey="Farshadpour F">F Farshadpour</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cox, Dr" uniqKey="Cox D">DR Cox</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Benjamini, Y" uniqKey="Benjamini Y">Y Benjamini</name>
</author>
<author><name sortKey="Hochberg, Y" uniqKey="Hochberg Y">Y Hochberg</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Caroline du Nord</li>
<li>Pennsylvanie</li>
</region>
<settlement><li>Chapel Hill (Caroline du Nord)</li>
<li>Pittsburgh</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
<li>Université de Pittsburgh</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Californie"><name sortKey="Gross, Andrew M" sort="Gross, Andrew M" uniqKey="Gross A" first="Andrew M" last="Gross">Andrew M. Gross</name>
</region>
<name sortKey="Carter, Hannah" sort="Carter, Hannah" uniqKey="Carter H" first="Hannah" last="Carter">Hannah Carter</name>
<name sortKey="Choueiri, Michel" sort="Choueiri, Michel" uniqKey="Choueiri M" first="Michel" last="Choueiri">Michel Choueiri</name>
<name sortKey="Coffey, Charles S" sort="Coffey, Charles S" uniqKey="Coffey C" first="Charles S" last="Coffey">Charles S. Coffey</name>
<name sortKey="Cohen, Ezra E" sort="Cohen, Ezra E" uniqKey="Cohen E" first="Ezra E" last="Cohen">Ezra E. Cohen</name>
<name sortKey="Cohen, Ezra E" sort="Cohen, Ezra E" uniqKey="Cohen E" first="Ezra E" last="Cohen">Ezra E. Cohen</name>
<name sortKey="Egloff, Ann Marie" sort="Egloff, Ann Marie" uniqKey="Egloff A" first="Ann Marie" last="Egloff">Ann Marie Egloff</name>
<name sortKey="Grandis, Jennifer R" sort="Grandis, Jennifer R" uniqKey="Grandis J" first="Jennifer R" last="Grandis">Jennifer R. Grandis</name>
<name sortKey="Hayes, D Neil" sort="Hayes, D Neil" uniqKey="Hayes D" first="D. Neil" last="Hayes">D. Neil Hayes</name>
<name sortKey="Hofree, Matan" sort="Hofree, Matan" uniqKey="Hofree M" first="Matan" last="Hofree">Matan Hofree</name>
<name sortKey="Ideker, Trey" sort="Ideker, Trey" uniqKey="Ideker T" first="Trey" last="Ideker">Trey Ideker</name>
<name sortKey="Ideker, Trey" sort="Ideker, Trey" uniqKey="Ideker T" first="Trey" last="Ideker">Trey Ideker</name>
<name sortKey="Ideker, Trey" sort="Ideker, Trey" uniqKey="Ideker T" first="Trey" last="Ideker">Trey Ideker</name>
<name sortKey="Ideker, Trey" sort="Ideker, Trey" uniqKey="Ideker T" first="Trey" last="Ideker">Trey Ideker</name>
<name sortKey="Lippman, Scott M" sort="Lippman, Scott M" uniqKey="Lippman S" first="Scott M" last="Lippman">Scott M. Lippman</name>
<name sortKey="Lippman, Scott M" sort="Lippman, Scott M" uniqKey="Lippman S" first="Scott M" last="Lippman">Scott M. Lippman</name>
<name sortKey="Lippman, Scott M" sort="Lippman, Scott M" uniqKey="Lippman S" first="Scott M" last="Lippman">Scott M. Lippman</name>
<name sortKey="Nguyen, Quyen T" sort="Nguyen, Quyen T" uniqKey="Nguyen Q" first="Quyen T" last="Nguyen">Quyen T. Nguyen</name>
<name sortKey="Nguyen, Quyen T" sort="Nguyen, Quyen T" uniqKey="Nguyen Q" first="Quyen T" last="Nguyen">Quyen T. Nguyen</name>
<name sortKey="Orosco, Ryan K" sort="Orosco, Ryan K" uniqKey="Orosco R" first="Ryan K" last="Orosco">Ryan K. Orosco</name>
<name sortKey="Shen, John P" sort="Shen, John P" uniqKey="Shen J" first="John P" last="Shen">John P. Shen</name>
</country>
</tree>
</affiliations>
</record>

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Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

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