Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study

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Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread : a case control study

Lawler, Katherine (författare): Kings Coll London, Sch Canc Studies, CRUK Kings Hlth Partners Ctr, Guys Campus, London SE1 1UL, England.;Kings Coll London, Ins Math & Mol Biomed, Hodgkin Bldg,Guys Campus, London SE1 1UL, England.,King's College London

Papouli, Efterpi (författare): Guys & St Thomas NHS Fdn Trust, NIHR Comprehens Biomed Res Ctr, London WC2R 2LS, England.;Kings Coll London, London WC2R 2LS, England.,King's College London

Naceur-Lombardelli, Cristina (författare): Kings Coll London, Guys Hosp, Res Oncol, Fac Life Sci & Med, London SE1 9RT, England.,King's College London

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Mera, Anca (författare): Kings Coll London, Guys Hosp, Res Oncol, Fac Life Sci & Med, London SE1 9RT, England.;Kings Coll London, Guys Hosp, Canc Epidemiol Unit, London SE1 9RT, England.,King's College London

Ougham, Kayleigh (författare): Kings Coll London, Guys Hosp, Canc Bioinformat, Innovat Ctr,Canc Ctr, London SE1 9RT, England.,King's College London

Tutt, Andrew (författare): King's College London

Kimbung, Siker (författare): Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Kings Coll London, Breast Canc Now Res Unit, Kings Hlth Partners AHSC, Canc Ctr,Guys Hosp,Innovat Ctr,Fac Life Sci & Med, London SE1 9RT, England.;Lund Univ, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.

Hedenfalk, Ingrid (författare): Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Kings Coll London, Breast Canc Now Res Unit, Kings Hlth Partners AHSC, Canc Ctr,Guys Hosp,Innovat Ctr,Fac Life Sci & Med, London SE1 9RT, England.;Lund Univ, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.

Zhan, Jun (författare): Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China.;Peking Univ, Dept Anat Histol & Embryol, Lab Mol Cell Biol & Tumor Biol, Hlth Sci Ctr, Beijing, Peoples R China.,Peking University,Ministry of Education, China

Zhang, Hongquan (författare): Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Beijing, Peoples R China.;Peking Univ, Dept Anat Histol & Embryol, Lab Mol Cell Biol & Tumor Biol, Hlth Sci Ctr, Beijing, Peoples R China.,Peking University,Ministry of Education, China

Buus, Richard (författare): Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London, England.,Institute of Cancer Research London

Dowsett, Mitch (författare): Inst Canc Res, Breast Canc Now Toby Robins Res Ctr, London, England.,Institute of Cancer Research London

Ng, Tony (författare): Kings Coll London, Sch Canc Studies, CRUK Kings Hlth Partners Ctr, Guys Campus, London SE1 1UL, England.;Kings Coll London, Richard Dimbleby Dept Canc Res, Randall Div Cell & Mol Biophys, Guys Campus, London SE1 1UL, England.;UCL, UCL Canc Inst, Paul OGorman Bldg, London WC1E 6DD, England.,King's College London,UCL Cancer Institute

Pinder, Sarah E. (författare): Kings Coll London, Guys Hosp, Res Oncol, Fac Life Sci & Med, London SE1 9RT, England.,Guy's and St Thomas' NHS Foundation Trust

Parker, Peter (författare): Kings Coll London, Sch Canc Studies, CRUK Kings Hlth Partners Ctr, Guys Campus, London SE1 1UL, England.;London Res Inst, Lincolns Inn Fields, London WC2A 3LY, England.

Holmberg, Lars (författare): Uppsala universitet,Endokrinkirurgi,Kings Coll London, Guys Hosp, Canc Epidemiol Unit, London SE1 9RT, England,Uppsala University Hospital,King's College London

Gillett, Cheryl E. (författare): Kings Coll London, Guys Hosp, Res Oncol, Fac Life Sci & Med, London SE1 9RT, England.,Guy's and St Thomas' NHS Foundation Trust

Grigoriadis, Anita (författare): Kings Coll London, Sch Canc Studies, CRUK Kings Hlth Partners Ctr, Guys Campus, London SE1 1UL, England.;Kings Coll London, Guys Hosp, Res Oncol, Fac Life Sci & Med, London SE1 9RT, England.;Kings Coll London, Guys Hosp, Canc Bioinformat, Innovat Ctr,Canc Ctr, London SE1 9RT, England.,King's College London,Guy's and St Thomas' NHS Foundation Trust

Purushotham, Arnie (författare): Kings Coll London, Sch Canc Studies, CRUK Kings Hlth Partners Ctr, Guys Campus, London SE1 1UL, England.;Kings Coll London, Guys Hosp, Res Oncol, Fac Life Sci & Med, London SE1 9RT, England.,Guy's and St Thomas' NHS Foundation Trust

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Kings Coll London, Sch Canc Studies, CRUK Kings Hlth Partners Ctr, Guys Campus, London SE1 1UL, England;Kings Coll London, Ins Math & Mol Biomed, Hodgkin Bldg,Guys Campus, London SE1 1UL, England. King's College London (creator_code:org_t)

2017-10-13
2017
Engelska.
Ingår i: Breast Cancer Research. - : BIOMED CENTRAL LTD. - 1465-5411 .- 1465-542X. ; 19

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://uu.diva-port... (primary) (Raw object); https://breast-cance...; http://dx.doi.org/10... (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://lup.lub.lu.s...; visa färre...

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Background: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.Methods: A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Whole-genome expression profiles were obtained using whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE) samples. A systematic protocol was developed for handling FFPE samples together with stringent data quality controls to identify robust expression profiling data. A panel of published and novel gene sets were tested for association with these specific patterns of metastatic spread and odds ratios (ORs) were calculated.Results: Metasynchronous metastasis to bone and viscera was found in all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined receptor status and specific IntClust subgroups were risk factors for visceral-only or bone-only first metastases. Among gene modules, those related to proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3 (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV) was identified in estrogen-receptor-positive breast cancers with metasynchronous metastasis to bone and viscera (area under the curve = 0.77), and its expression increased the risk of bone and visceral metasynchronous spread in this population. BV was further orthogonally validated with NanoString nCounter in primary breast cancers, and was reproducible in their matched lymph nodes metastases and an external cohort.Conclusion: This case-control study of WG-DASL global expression profiles from FFPE tumour samples, after careful quality control and RNA selection, revealed that gene modules in the primary tumour have differing risks for clinical patterns of metasynchronous first metastases. Moreover, a novel gene module was identified as a putative risk factor for metasynchronous bone and visceral first metastatic spread, with potential implications for disease monitoring and treatment planning.

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Artiklar i publikationen: Breast Cancer Re ...

Av lärosätet: Uppsala universitet; Lunds universitet

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Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread : a case control study

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