• Something wrong with this record ?

The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples

JE. Barrett, C. Herzog, A. Jones, OC. Leavy, I. Evans, S. Knapp, D. Reisel, T. Nazarenko, YN. Kim, D. Franchi, A. Ryan, J. Franks, L. Bjørge, M. Zikan, D. Cibula, N. Harbeck, N. Colombo, F. Dudbridge, L. Jones, K. Sundström, J. Dillner, AF....

. 2022 ; 13 (1) : 449. [pub] 20220201

Language English Country Great Britain

Document type Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22011203

Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women's risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80-0.88) and 0.81 (95% CI: 0.76-0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.

Breast Center Department of Obstetrics and Gynecology University of Munich Munich Germany

Breast Service University College London Hospital London UK

Centre for Cancer Biomarkers CCBIO Department of Clinical Science University of Bergen Bergen Norway

Centre for Tumour Biology Department Barts Cancer Institute Queen Mary University of London London UK

Department of Applied Health Research University College London London UK

Department of Gynecology and Obstetrics 1st Faculty of Medicine Charles University Prague University Hospital Bulovka Prague Czech Republic

Department of Health Sciences University of Leicester Leicester LE1 7RH UK

Department of Laboratory Medicine Division of Pathology Karolinska Institutet Stockholm Sweden

Department of Non communicable Disease Epidemiology London School of Hygiene and Tropical Medicine London UK

Department of Obstetrics and Gynaecology Haukeland University Hospital Bergen Norway

Department of Women's and Children's Health Karolinska Institutet and Karolinska University Hospital Stockholm Sweden

Department of Women's Cancer University College London London UK

European Translational Oncology Prevention and Screening Institute Universität Innsbruck Innsbruck Austria Hall in Tirol Austria

Gynaecologic Oncology Center Department of Obstetrics and Gynecology 1st Faculty of Medicine Charles University Prague General University Hospital Prague Prague Czech Republic

Institute for Biomedical Aging Research Universität Innsbruck Innsbruck Austria

Istituto Europeo di Oncologia IRCCS Milan Italy

University of Milano Bicocca Milan Italy

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22011203
003      
CZ-PrNML
005      
20220506131246.0
007      
ta
008      
220425s2022 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/s41467-021-27918-w $2 doi
035    __
$a (PubMed)35105882
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Barrett, James E $u European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria $u Department of Women's Cancer, University College London, London, UK $u Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria
245    14
$a The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples / $c JE. Barrett, C. Herzog, A. Jones, OC. Leavy, I. Evans, S. Knapp, D. Reisel, T. Nazarenko, YN. Kim, D. Franchi, A. Ryan, J. Franks, L. Bjørge, M. Zikan, D. Cibula, N. Harbeck, N. Colombo, F. Dudbridge, L. Jones, K. Sundström, J. Dillner, AF. Rådestad, K. Gemzell-Danielsson, N. Pashayan, M. Widschwendter
520    9_
$a Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women's risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80-0.88) and 0.81 (95% CI: 0.76-0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.
650    _2
$a nádorové biomarkery $x genetika $x metabolismus $7 D014408
650    _2
$a prsy $x cytologie $x metabolismus $7 D001940
650    _2
$a nádory prsu $x genetika $x metabolismus $7 D001943
650    _2
$a cervix uteri $x cytologie $x metabolismus $7 D002584
650    _2
$a CpG ostrůvky $7 D018899
650    12
$a metylace DNA $7 D019175
650    _2
$a epigenom $7 D000081122
650    _2
$a epigenomika $x metody $7 D057890
650    _2
$a epitelové buňky $x metabolismus $7 D004847
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a lidé $7 D006801
650    _2
$a mutace $7 D009154
650    _2
$a prognóza $7 D011379
650    _2
$a ROC křivka $7 D012372
655    _2
$a hodnotící studie $7 D023362
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Herzog, Chiara $u European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria $u Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria $1 https://orcid.org/000000021572498X
700    1_
$a Jones, Allison $u Department of Women's Cancer, University College London, London, UK
700    1_
$a Leavy, Olivia C $u Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK $u Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK $1 https://orcid.org/0000000215035535
700    1_
$a Evans, Iona $u Department of Women's Cancer, University College London, London, UK
700    1_
$a Knapp, Susanne $u Department of Women's Cancer, University College London, London, UK
700    1_
$a Reisel, Daniel $u Department of Women's Cancer, University College London, London, UK
700    1_
$a Nazarenko, Tatiana $u Department of Women's Cancer, University College London, London, UK $1 https://orcid.org/0000000242457346
700    1_
$a Kim, Yoo-Na $u European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria $u Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria $1 https://orcid.org/0000000202023228
700    1_
$a Franchi, Dorella $u Istituto Europeo di Oncologia, IRCCS, Milan, Italy
700    1_
$a Ryan, Andy $u Department of Women's Cancer, University College London, London, UK
700    1_
$a Franks, Joanna $u Breast Service, University College London Hospital, London, UK
700    1_
$a Bjørge, Line $u Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway $u Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway
700    1_
$a Zikan, Michal $u Department of Gynecology and Obstetrics, First Faculty of Medicine, Charles University in Prague, University Hospital Bulovka, Prague, Czech Republic $1 https://orcid.org/0000000152668895 $7 xx0096708
700    1_
$a Cibula, David $u Gynaecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, Prague, Czech Republic $1 https://orcid.org/0000000163879356 $7 jo20000074072
700    1_
$a Harbeck, Nadia $u Breast Center, Department of Obstetrics and Gynecology, University of Munich (LMU), Munich, Germany $1 https://orcid.org/0000000297447372
700    1_
$a Colombo, Nicoletta $u Istituto Europeo di Oncologia, IRCCS, Milan, Italy $u University of Milano-Bicocca, Milan, Italy
700    1_
$a Dudbridge, Frank $u Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK $u Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK $1 https://orcid.org/0000000288178908
700    1_
$a Jones, Louise $u Centre for Tumour Biology Department, Barts Cancer Institute, Queen Mary University of London, London, UK
700    1_
$a Sundström, Karin $u Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden
700    1_
$a Dillner, Joakim $u Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden $1 https://orcid.org/0000000185886506
700    1_
$a Rådestad, Angelique Flöter $u Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
700    1_
$a Gemzell-Danielsson, Kristina $u Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden $1 https://orcid.org/0000000165161444
700    1_
$a Pashayan, Nora $u Department of Applied Health Research, University College London, London, UK $1 https://orcid.org/0000000308432468
700    1_
$a Widschwendter, Martin $u European Translational Oncology Prevention and Screening (EUTOPS) Institute, Universität Innsbruck, Innsbruck, Austria, Hall in Tirol, Austria. martin.widschwendter@uibk.ac.at $u Department of Women's Cancer, University College London, London, UK. martin.widschwendter@uibk.ac.at $u Institute for Biomedical Aging Research, Universität Innsbruck, Innsbruck, Austria. martin.widschwendter@uibk.ac.at $u Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. martin.widschwendter@uibk.ac.at $1 https://orcid.org/0000000277788380
773    0_
$w MED00184850 $t Nature communications $x 2041-1723 $g Roč. 13, č. 1 (2022), s. 449
856    41
$u https://pubmed.ncbi.nlm.nih.gov/35105882 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220425 $b ABA008
991    __
$a 20220506131238 $b ABA008
999    __
$a ok $b bmc $g 1789019 $s 1162401
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 13 $c 1 $d 449 $e 20220201 $i 2041-1723 $m Nature communications $n Nat Commun $x MED00184850
LZP    __
$a Pubmed-20220425

Find record

Citation metrics

Archiving options