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Sökning: onr:"swepub:oai:DiVA.org:oru-57398" > TP53-based interact...

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer.

Fagerholm, Rainer, (författare)
Helsinki University Hospital, Helsinki, Finland
Khan, Sofia, (författare)
Helsinki University Hospital, Helsinki, Finland
Schmidt, Marjanka K, (författare)
Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
visa fler...
García-Closas, Montserrat, (författare)
National Cancer Institute, Rockville MD, United States
Heikkilä, Päivi, (författare)
Helsinki University Hospital, Helsinki, Finland
Saarela, Jani, (författare)
University of Helsinki, Helsinki, Finland
Beesley, Jonathan, (författare)
QIMR Berghofer Medical Research Institute, Brisbane, Australia
Jamshidi, Maral, (författare)
Helsinki University Hospital, Helsinki, Finland
Aittomäki, Kristiina, (författare)
Helsinki University Hospital, Helsinki, Finland
Liu, Jianjun, (författare)
Genome Institute of Singapore, Biopolis, Singapore
Ali, H Raza, (författare)
University of Cambridge, Cambridge, United Kingdom
Andrulis, Irene L, (författare)
Mount Sinai Hospital, Toronto, Canada; University of Toronto, Toronto, Canada
Beckmann, Matthias W, (författare)
University Hospital Erlangen, Erlangen, Germany
Behrens, Sabine, (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany
Blows, Fiona M, (författare)
University of Cambridge, Cambridge, United Kingdom
Brenner, Hermann, (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany
Chang-Claude, Jenny, (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany; University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Couch, Fergus J, (författare)
University of Helsinki, Helsinki, Finland
Czene, Kamila, (författare)
Karolinska Institutet, Stockholm, Sweden
Fasching, Peter A, (författare)
Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany; University of California at Los Angeles, Los Angeles CA, United States
Figueroa, Jonine, (författare)
National Cancer Institute, Rockville MD, United States; The University of Edinburgh Medical School, Edinburgh, United Kingdom
Floris, Giuseppe, (författare)
University Hospitals Leuven, Leuven, Belgium
Glendon, Gord, (författare)
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada
Guo, Qi, (författare)
University of Cambridge, Cambridge, United Kingdom
Hall, Per, (författare)
Karolinska Institutet, Stockholm, Sweden
Hallberg, Emily, (författare)
Mayo Clinic, Rochester MN, United States
Hamann, Ute, (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany
Holleczek, Bernd, (författare)
Saarland Cancer Registry, Saarbrücken, Germany
Hooning, Maartje J, (författare)
University of Helsinki, Helsinki, Finland; Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
Hopper, John L, (författare)
University of Helsinki, Helsinki, Finland; National Cancer Institute, Rockville MD, United States
Jager, Agnes, (författare)
University of Helsinki, Helsinki, Finland; Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
Kabisch, Maria, (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany
Keeman, Renske, (författare)
Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
Kosma, Veli-Matti, (författare)
The University of Melbourne, Melbourne, Australia; University of Eastern Finland, Kuopio, Finland; University of Eastern Finland, Kuopio, Finland; Kuopio University Hospital, Kuopio, Finland
Lambrechts, Diether, (författare)
Vesalius Research Center, Leuven, Belgium; University of Leuven, Leuven, Belgium
Lindblom, Annika, (författare)
Karolinska Institutet, Stockholm, Sweden
Mannermaa, Arto, (författare)
University of Eastern Finland, Kuopio, Finland; University of Eastern Finland, Kuopio, Finland; Kuopio University Hospital, Kuopio, Finland
Margolin, Sara, (författare)
Karolinska Institutet, Stockholm, Sweden
Provenzano, Elena, (författare)
Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom
Shah, Mitul, (författare)
University of Cambridge, Cambridge, United Kingdom
Southey, Melissa C, (författare)
The University of Melbourne, Melbourne, Australia
Dennis, Joe, (författare)
University of Cambridge, Cambridge, United Kingdom
Lush, Michael, (författare)
University of Cambridge, Cambridge, United Kingdom
Michailidou, Kyriaki, (författare)
University of Cambridge, Cambridge, United Kingdom; The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
Wang, Qin, (författare)
University of Cambridge, Cambridge, United Kingdom
Bolla, Manjeet K, (författare)
University of Cambridge, Cambridge, United Kingdom
Dunning, Alison M, (författare)
University of Cambridge, Cambridge, United Kingdom
Easton, Douglas F, (författare)
University of Cambridge, Cambridge, United Kingdom;
Pharoah, Paul D P, (författare)
University of Cambridge, Cambridge, United Kingdom
Chenevix-Trench, Georgia, (författare)
QIMR Berghofer Medical Research Institute, Brisbane, Australia
Blomqvist, Carl, (författare)
Region Örebro län, University of Helsinki, Helsinki, Finland
Nevanlinna, Heli, (författare)
University of Helsinki, Helsinki, Finland
Garcia-Closas, M (författare)
Heikkila, P (författare)
Aittomaki, K (författare)
visa färre...
Region Örebro län (creator_code:org_t)
2017
Engelska.
Ingår i: OncoTarget. - Impact press. - 1949-2553. ; 8:11, s. 18381-18398
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes.In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 × 10-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 × 10-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines.If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Onkologi
Oncology
SNP
TP53
anthracycline
breast cancer
survival

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