Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24980573
TITLE
Identification of a melanoma susceptibility locus and somatic mutation in TET2.
ABSTRACT
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.
DATE PUBLISHED
2014 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2014/06/30
entrez 2014/07/02 06:00
pubmed 2014/07/02 06:00
medline 2014/10/22 06:00
AUTHORS
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 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 Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hayward NK Hayward Nicholas K NK Oncogenomics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia.
Hunter DJ Hunter David J DJ 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.
INVESTIGATORS
JOURNAL
VOLUME: 35
ISSUE: 9
TITLE: Carcinogenesis
ISOABBREVIATION: Carcinogenesis
YEAR: 2014
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1460-2180
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Carcinogenesis
COUNTRY: England
ISSNLINKING: 0143-3334
NLMUNIQUEID: 8008055
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
10589 Cancer Research UK United Kingdom
5P50CA093459-10 NCI NIH HHS United States
CA122838 NCI NIH HHS United States
CA167552 NCI NIH HHS United States
CA176726 NCI NIH HHS United States
CA49449 NCI NIH HHS United States
CA67262 NCI NIH HHS United States
CA87969 NCI NIH HHS United States
P30 CA016672 NCI NIH HHS United States
P30 CA023108 NCI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Case-Control Studies
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
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 DNA-Binding Proteins
0 Proto-Oncogene Proteins
0 TET2 protein, human
OTHER ID's
OTHERID SOURCE
PMC4146422 NLM