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Spatio-temporal ana...
Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones
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- Marklund, Maja (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- Schultz, Niklas (author)
- Karolinska Institutet
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- Friedrich, Stefanie, 1973- (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Lab, Solna, Sweden.
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- Berglund, Emelie (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- Tarish, Firas (author)
- Karolinska Inst, Div Translat Med & Chem Biol, Sci Life Lab, Solna, Sweden.
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- Tanoglidi, Anna (author)
- Evangelismos Gen Hosp, Dept Pathol, 45-47 Ipsilantou Str, Athens, Greece.
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- Liu, Yao (author)
- Karolinska Inst, Div Translat Med & Chem Biol, Sci Life Lab, Solna, Sweden.
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- Bergenstråhle, Ludvig (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab
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- Erickson, Andrew (author)
- Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
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- Helleday, Thomas (author)
- Karolinska Institutet
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- Lamb, Alastair D. (author)
- Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
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- Sonnhammer, Erik L. L. (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Lab, Solna, Sweden.
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- Lundeberg, Joakim (author)
- KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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(creator_code:org_t)
- 2022-09-17
- 2022
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Abstract
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- The molecular mechanisms underlying lethal castration-resistant prostate cancer remain poorly understood, with intratumoral heterogeneity a likely contributing factor. To examine the temporal aspects of resistance, we analyze tumor heterogeneity in needle biopsies collected before and after treatment with androgen deprivation therapy. By doing so, we are able to couple clinical responsiveness and morphological information such as Gleason score to transcriptome-wide data. Our data-driven analysis of transcriptomes identifies several distinct intratumoral cell populations, characterized by their unique gene expression profiles. Certain cell populations present before treatment exhibit gene expression profiles that match those of resistant tumor cell clusters, present after treatment. We confirm that these clusters are resistant by the localization of active androgen receptors to the nuclei in cancer cells post-treatment. Our data also demonstrates that most stromal cells adjacent to resistant clusters do not express the androgen receptor, and we identify differentially expressed genes for these cells. Altogether, this study shows the potential to increase the power in predicting resistant tumors. Spatial heterogeneity in prostate cancer can contribute to its resistance to androgen deprivation therapy (ADT). Here, the authors analyse prostate cancer samples before and after ADT using Spatial Transcriptomics, and find heterogeneous pre-treatment tumour cell populations and stromal cells that are associated with resistance.
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)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- By the author/editor
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Marklund, Maja
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Schultz, Niklas
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Friedrich, Stefa ...
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Berglund, Emelie
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Tarish, Firas
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Tanoglidi, Anna
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Liu, Yao
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Bergenstråhle, L ...
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Erickson, Andrew
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Helleday, Thomas
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Lamb, Alastair D ...
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Sonnhammer, Erik ...
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Lundeberg, Joaki ...
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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 ...
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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 Pediatrics
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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 Cell and Molecul ...
- Articles in the publication
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Nature Communica ...
- By the university
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Royal Institute of Technology
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Stockholm University
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Karolinska Institutet