title: Progressive APOBEC3B mRNA expression in distant breast cancer metastases.
abstract: BACKGROUND
  APOBEC3B was recently identified as a gain-of-function enzymatic source of mutagenesis, which may offer novel therapeutic options with molecules that specifically target this enzyme. In primary breast cancer, APOBEC3B mRNA is deregulated in a substantial proportion of cases and its expression is associated with poor prognosis. However, its expression in breast cancer metastases, which are the main causes of breast cancer-related death, remained to be elucidated.
  
  
  METHODS
  RNA was isolated from 55 primary breast cancers and paired metastases, including regional lymph node (N = 20) and distant metastases (N = 35). APOBEC3B mRNA levels were measured by RT-qPCR. Expression levels of the primary tumors and corresponding metastases were compared, including subgroup analysis by estrogen receptor (ER/ESR1) status.
  
  
  RESULTS
  Overall, APOBEC3B mRNA levels of distant metastases were significantly higher as compared to the corresponding primary breast tumor (P = 0.0015), an effect that was not seen for loco-regional lymph node metastases (P = 0.23). Subgroup analysis by ER-status showed that increased APOBEC3B levels in distant metastases were restricted to metastases arising from ER-positive primary breast cancers (P = 0.002). However, regarding ER-negative primary tumors, only loco-regional lymph node metastases showed increased APOBEC3B expression when compared to the corresponding primary tumor (P = 0.028).
  
  
  CONCLUSIONS
  APOBEC3B mRNA levels are significantly higher in breast cancer metastases as compared to the corresponding ER-positive primary tumors. This suggests a potential role for APOBEC3B in luminal breast cancer progression, and consequently, a promising role for anti-APOBEC3B therapies in advanced stages of this frequent form of breast cancer.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.|Cancer Genomics Center, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Anieta M
authors.identifier: http://orcid.org/0000-0003-1341-5400
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Willemijne A M E
authors.initials: WA
authors.lastname: Schrijver
authors.affiliation: Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Simone U
authors.initials: SU
authors.lastname: Dalm
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Vanja
authors.initials: V
authors.lastname: de Weerd
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cathy B
authors.initials: CB
authors.lastname: Moelans
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Natalie
authors.initials: N
authors.lastname: Ter Hoeve
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.|Cancer Genomics Center, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Carolien H M
authors.initials: CH
authors.lastname: van Deurzen
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics*; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D003564:Cytidine Deaminase; D047628:Estrogen Receptor alpha; D015778:Minor Histocompatibility Antigens; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C506487:ESR1 protein, human; C508053:ERBB2 protein, human; C495794:APOBEC3B protein, human