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Genetic interaction...
Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development
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- Li, Yafang (author)
- Baylor College of Medicine
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Xiao, Xiangjun (author)
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Bossé, Yohan (author)
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Gorlova, Olga (author)
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Gorlov, Ivan (author)
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Han, Younghun (author)
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Byun, Jinyoung (author)
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Leighl, Natasha (author)
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Johansen, Jakob S. (author)
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Barnett, Matt (author)
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Chen, Chu (author)
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Goodman, Gary (author)
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Cox, Angela (author)
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Taylor, Fiona (author)
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Woll, Penella (author)
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Wichmann, H. Erich (author)
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Manz, Judith (author)
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Muley, Thomas (author)
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Risch, Angela (author)
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Rosenberger, Albert (author)
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Han, Jiali (author)
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Siminovitch, Katherine (author)
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Arnold, Susanne M. (author)
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Haura, Eric B. (author)
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Bolca, Ciprian (author)
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Holcatova, Ivana (author)
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Janout, Vladimir (author)
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Kontic, Milica (author)
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Lissowska, Jolanta (author)
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Mukeria, Anush (author)
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Ognjanovic, Simona (author)
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Orlowski, Tadeusz M. (author)
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Scelo, Ghislaine (author)
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Swiatkowska, Beata (author)
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Zaridze, David (author)
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Bakke, Per (author)
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Skaug, Vidar (author)
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Zienolddiny, Shanbeh (author)
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Duell, Eric J. (author)
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Butler, Lesley M. (author)
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Houlston, Richard (author)
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Artigas, María Soler (author)
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- Grankvist, Kjell (author)
- Umeå universitet,Klinisk kemi
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- Johansson, Mikael (author)
- Umeå universitet,Onkologi
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Shepherd, Frances A. (author)
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Marcus, Michael W. (author)
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- Brunnström, Hans (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups
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- Manjer, Jonas (author)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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Muller, David C. (author)
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Overvad, Kim (author)
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Trichopoulou, Antonia (author)
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Tumino, Rosario (author)
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Liu, Geoffrey (author)
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Bojesen, Stig E. (author)
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Wu, Xifeng (author)
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Le Marchand, Loic (author)
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Albanes, Demetrios (author)
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Bickeböller, Heike (author)
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Aldrich, Melinda C. (author)
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Bush, William S. (author)
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Tardon, Adonina (author)
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Rennert, Gad (author)
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Teare, M. Dawn (author)
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Field, John K. (author)
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Kiemeney, Lambertus A. (author)
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Lazarus, Philip (author)
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Haugen, Aage (author)
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Lam, Stephen (author)
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Schabath, Matthew B. (author)
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Andrew, Angeline S. (author)
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Bertazzi, Pier Alberto (author)
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Pesatori, Angela C. (author)
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Christiani, David C. (author)
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Caporaso, Neil (author)
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Johansson, Mattias (author)
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McKay, James D. (author)
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Brennan, Paul (author)
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Hung, Rayjean J. (author)
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- Amos, Christopher I. (author)
- Dartmouth College
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(creator_code:org_t)
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et al
- 2019-03-05
- 2019
- English.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 10:19, s. 1760-1774
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://www.oncotarg...
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
Close
- The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- epistasis
- functional annotation
- lung cancer
- oncogenesis
- Epistasis
- Functional annotation
- Lung cancer
- Oncogenesis
Publication and Content Type
- ref (subject category)
- art (subject category)
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Oncotarget
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To the university's database
- By the author/editor
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Li, Yafang
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Xiao, Xiangjun
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Bossé, Yohan
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Gorlova, Olga
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Gorlov, Ivan
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Han, Younghun
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show more...
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Byun, Jinyoung
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Leighl, Natasha
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Johansen, Jakob ...
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Barnett, Matt
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Chen, Chu
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Goodman, Gary
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Cox, Angela
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Taylor, Fiona
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Woll, Penella
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Wichmann, H. Eri ...
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Manz, Judith
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Muley, Thomas
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Risch, Angela
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Rosenberger, Alb ...
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Han, Jiali
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Siminovitch, Kat ...
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Arnold, Susanne ...
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Haura, Eric B.
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Bolca, Ciprian
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Holcatova, Ivana
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Janout, Vladimir
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Kontic, Milica
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Lissowska, Jolan ...
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Mukeria, Anush
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Ognjanovic, Simo ...
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Orlowski, Tadeus ...
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Scelo, Ghislaine
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Swiatkowska, Bea ...
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Zaridze, David
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Bakke, Per
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Skaug, Vidar
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Zienolddiny, Sha ...
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Duell, Eric J.
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Butler, Lesley M ...
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Houlston, Richar ...
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Artigas, María S ...
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Grankvist, Kjell
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Johansson, Mikae ...
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Shepherd, France ...
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Marcus, Michael ...
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Brunnström, Hans
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Manjer, Jonas
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Melander, Olle
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Muller, David C.
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Overvad, Kim
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Trichopoulou, An ...
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Tumino, Rosario
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Liu, Geoffrey
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Bojesen, Stig E.
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Wu, Xifeng
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Le Marchand, Loi ...
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Albanes, Demetri ...
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Bickeböller, Hei ...
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Aldrich, Melinda ...
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Bush, William S.
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Tardon, Adonina
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Rennert, Gad
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Teare, M. Dawn
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Field, John K.
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Kiemeney, Lamber ...
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Lazarus, Philip
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Haugen, Aage
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Lam, Stephen
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Schabath, Matthe ...
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Andrew, Angeline ...
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Bertazzi, Pier A ...
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Pesatori, Angela ...
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Christiani, Davi ...
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Caporaso, Neil
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Johansson, Matti ...
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McKay, James D.
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Brennan, Paul
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Hung, Rayjean J.
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Amos, Christophe ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Oncotarget
- By the university
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Umeå University
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Lund University