title: The histone chaperone HJURP is a new independent prognostic marker for luminal A breast carcinoma.
abstract: BACKGROUND
  Breast cancer is a heterogeneous disease with different molecular subtypes that have varying responses to therapy. An ongoing challenge in breast cancer research is to distinguish high-risk patients from good prognosis patients. This is particularly difficult in the low-grade, ER-positive luminal A tumors, where robust diagnostic tools to aid clinical treatment decisions are lacking. Recent data implicating chromatin regulators in cancer initiation and progression offers a promising avenue to develop new tools to help guide clinical decisions.
  
  
  METHODS
  Here we exploit a published transcriptome dataset and an independent validation cohort to correlate the mRNA expression of selected chromatin regulators with respect to the four intrinsic breast cancer molecular subtypes. We then perform univariate and multivariate analyses to compare the prognostic value of a panel of chromatin regulators to Ki67, a currently utilized proliferation marker.
  
  
  RESULTS
  Unsupervised hierarchical clustering revealed a gene cluster containing several histone chaperones and histone variants highly-expressed in the proliferative subtypes (basal-like, HER2-positive, luminal B) but not in the luminal A subtype. Several chromatin regulators, including the histone chaperones CAF-1 (subunits p150 and p60), ASF1b, and HJURP, and the centromeric histone variant CENP-A, associated with local and metastatic relapse and poor patient outcome. Importantly, we find that HJURP can discriminate favorable and unfavorable outcome within the luminal A subtype, outperforming the currently utilized proliferation marker Ki67, as an independent prognostic marker for luminal A patients.
  
  
  CONCLUSIONS
  The integration of chromatin regulators as clinical biomarkers, in particular the histone chaperone HJURP, will help guide patient substratification and treatment options for low-risk luminal A breast carcinoma patients.
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: Rocio.Montes-De-Oca@curie.fr.
authors.forename: Rocío
authors.initials: R
authors.lastname: Montes de Oca
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: zachary.gurard-levin@curie.fr.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Gurard-Levin
authors.affiliation: Sorbonne University, PSL*, France; Institut Curie, U900, Paris F-75248, France; INSERM, U900, Mines Paris-Tech, Paris F-75248, France; Institut Curie, Department of Biostatistics, Paris F-75248, France. Electronic address: frederique.berger@curie.fr.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Berger
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: haniya.rehman@gmail.com.
authors.forename: Haniya
authors.initials: H
authors.lastname: Rehman
authors.affiliation: Institut Curie, Investigative Pathology Platform, Paris F-75248, France. Electronic address: elise.martel@curie.fr.
authors.forename: Elise
authors.initials: E
authors.lastname: Martel
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: armelle.corpet@univ-lyon1.fr.
authors.forename: Armelle
authors.initials: A
authors.lastname: Corpet
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: Leanne.De-Koning@curie.fr.
authors.forename: Leanne
authors.initials: L
authors.lastname: de Koning
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: isabelle.vassias@curie.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vassias
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: laurence.wilson@curie.fr.
authors.forename: Laurence O W
authors.initials: LO
authors.lastname: Wilson
authors.affiliation: Institut Curie, Investigative Pathology Platform, Paris F-75248, France. Electronic address: didier.meseure@curie.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Meseure
authors.affiliation: Institut Curie, Department of Surgery, Paris F-75248, France. Electronic address: fabien.reyal@curie.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.affiliation: Institut Curie, U900, Paris F-75248, France; INSERM, U900, Mines Paris-Tech, Paris F-75248, France; Institut Curie, Department of Biostatistics, Paris F-75248, France. Electronic address: alexia.savignoni@curie.fr.
authors.forename: Alexia
authors.initials: A
authors.lastname: Savignoni
authors.affiliation: Institut Curie, U900, Paris F-75248, France; INSERM, U900, Mines Paris-Tech, Paris F-75248, France; Institut Curie, Department of Biostatistics, Paris F-75248, France. Electronic address: bernard.asselain@curie.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.affiliation: Institut Curie, Department of Pathology, Paris F-75248, France. Electronic address: xavier.sastre@curie.fr.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.affiliation: Institut Curie, Centre de Recherche, Paris F-75248, France; CNRS, UMR3664, Paris F-75248, France; Equipe Labellisée Ligue contre le Cancer, UMR3664, Paris F-75248, France; UPMC, UMR3664, Paris F-75248, France; Sorbonne University, PSL*, France. Electronic address: Genevieve.Almouzni@curie.fr.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Almouzni
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D016000:Cluster Analysis; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D064111:Minichromosome Maintenance Complex Component 2 / Q000378:metabolism; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C491640:ASF1B protein, human; D001324:Autoantigens; D014408:Biomarkers, Tumor; C000619700:CENPA protein, human; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D012333:RNA, Messenger; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2
keywords: Biomarkers; CENP-A; Chromatin; Epigenetics; MKI67; Prognosis