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| PMID |
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| TITLE |
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| Identification of a melanoma susceptibility locus and somatic mutation in TET2. |
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| ABSTRACT |
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| Although genetic studies have reported a number of loci associated with melanoma risk, the complex genetic architecture of the disease is not yet fully understood. We sought to identify common genetic variants associated with melanoma risk in a genome-wide association study (GWAS) of 2298 cases and 6654 controls. Thirteen of 15 known loci were replicated with nominal significance. A total of 69 single-nucleotide polymorphisms (SNPs) were selected for in silico replication in two independent melanoma GWAS datasets (a total of 5149 cases and 12 795 controls). Seven novel loci were nominally significantly associated with melanoma risk. These seven SNPs were further genotyped in 234 melanoma cases and 238 controls. The SNP rs4698934 was nominally significantly associated with melanoma risk. The combined odds ratio per T allele = 1.18; 95% confidence interval (1.10-1.25); combined P = 7.70 × 10(-) (7). This SNP is located in the intron of the TET2 gene on chromosome 4q24. In addition, a novel somatic mutation of TET2 was identified by next-generation sequencing in 1 of 22 sporadic melanoma cases. TET2 encodes a member of TET family enzymes that oxidizes 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). It is a putative epigenetic biomarker of melanoma as we previously reported, with observation of reduced TET2 transcriptional expression. This study is the first to implicate TET2 genetic variation and mutation in melanoma. |
| © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| entrez |
2014/07/02 06:00 |
| pubmed |
2014/07/02 06:00 |
| medline |
2014/10/22 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Song F |
|
Song |
Fengju |
F |
|
Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China. |
| Amos CI |
|
Amos |
Christopher I |
CI |
|
Department of Community and Family Medicine, Center for Genomic Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755, USA. |
| Lee JE |
|
Lee |
Jeffrey E |
JE |
|
Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA. |
| Lian CG |
|
Lian |
Christine G |
CG |
|
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
| Fang S |
|
Fang |
Shenying |
S |
|
Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA. |
| Liu H |
|
Liu |
Hongliang |
H |
|
Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA. |
| MacGregor S |
|
MacGregor |
Stuart |
S |
|
Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. |
| Iles MM |
|
Iles |
Mark M |
MM |
|
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK. |
| Law MH |
|
Law |
Matthew H |
MH |
|
Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. |
| Lindeman NI |
|
Lindeman |
Neal I |
NI |
|
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. |
| Duffy DL |
|
Duffy |
David L |
DL |
|
Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. |
| Cust AE |
|
Cust |
Anne E |
AE |
|
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, University of Melbourne, Melbourne, Victoria 3052, Australia, Cancer Epidemiology and Services Research, Sydney School of Public Health, University of Sydney, Sydney, New South Wales 2006, Australia. |
| Jenkins MA |
|
Jenkins |
Mark A |
MA |
|
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, University of Melbourne, Melbourne, Victoria 3052, Australia. |
| Whiteman DC |
|
Whiteman |
David C |
DC |
|
Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. |
| Kefford RF |
|
Kefford |
Richard F |
RF |
|
Westmead Institute of Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, New South Wales 2145, Australia. |
| Giles GG |
|
Giles |
Graham G |
GG |
|
Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria 3053, Australia. |
| Armstrong BK |
|
Armstrong |
Bruce K |
BK |
|
Cancer Epidemiology and Services Research, Sydney School of Public Health, University of Sydney, Sydney, New South Wales 2006, Australia. |
| Aitken JF |
|
Aitken |
Joanne F |
JF |
|
Viertel Centre for Research in Cancer Control, Cancer Council Queensland, Brisbane, Queensland 4004, Australia. |
| Hopper JL |
|
Hopper |
John L |
JL |
|
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, University of Melbourne, Melbourne, Victoria 3052, Australia. |
| Brown KM |
|
Brown |
Kevin M |
KM |
|
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA. |
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. |
| Mann GJ |
|
Mann |
Graham J |
GJ |
|
Westmead Institute of Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, New South Wales 2145, Australia. |
| Bishop DT |
|
Bishop |
D Timothy |
DT |
|
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK. |
| Bishop JA |
|
Bishop |
Julia A Newton |
JA |
|
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK. |
|
GenoMEL consortium |
|
|
|
|
|
| Kraft P |
|
Kraft |
Peter |
P |
|
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. |
| Qureshi AA |
|
Qureshi |
Abrar A |
AA |
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Channing Division of Network Medicine and Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. |
| Kanetsky PA |
|
Kanetsky |
Peter A |
PA |
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Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. |
| Hayward NK |
|
Hayward |
Nicholas K |
NK |
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Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia. |
| Hunter DJ |
|
Hunter |
David J |
DJ |
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Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. |
| Wei Q |
|
Wei |
Qingyi |
Q |
|
Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA, jialhan@iu.edu qingyi.wei@duke.edu. |
| Han J |
|
Han |
Jiali |
J |
|
Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA, Channing Division of Network Medicine and Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN 46202, USA, Simon Cancer Center, Indiana University, Indianapolis, IN 46202, USA and Department of Dermatology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA jialhan@iu.edu. |
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| INVESTIGATORS |
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| JOURNAL |
|
| VOLUME: 35 |
| ISSUE: 9 |
| TITLE: Carcinogenesis |
| ISOABBREVIATION: Carcinogenesis |
| YEAR: 2014 |
| MONTH: Sep |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1460-2180 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Carcinogenesis |
| COUNTRY: England |
| ISSNLINKING: 0143-3334 |
| NLMUNIQUEID: 8008055 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Meta-Analysis |
| Research Support, N.I.H., Extramural |
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| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| CA167552 |
NCI NIH HHS |
United States |
| P30 CA016672 |
NCI NIH HHS |
United States |
| CA87969 |
NCI NIH HHS |
United States |
| 5P50CA093459-10 |
NCI NIH HHS |
United States |
| CA49449 |
NCI NIH HHS |
United States |
| P30 CA023108 |
NCI NIH HHS |
United States |
| CA67262 |
NCI NIH HHS |
United States |
| 10589 |
Cancer Research UK |
United Kingdom |
| CA122838 |
NCI NIH HHS |
United States |
| CA176726 |
NCI NIH HHS |
United States |
|
| GENERAL NOTE |
|
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| KEYWORDS |
|
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| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Case-Control Studies |
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| DNA-Binding Proteins |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genome-Wide Association Study |
genetics |
| Humans |
genetics |
| Melanoma |
genetics |
| Mutation |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Proto-Oncogene Proteins |
genetics |
| Risk Factors |
genetics |
| Skin Neoplasms |
genetics |
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| SUPPLEMENTARY MESH |
|
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| GENE SYMBOLS |
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| CHEMICALS |
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| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
DNA-Binding Proteins |
| 0 |
Proto-Oncogene Proteins |
| 0 |
TET2 protein, human |
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| OTHER ID's |
|
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|
