title: Assessing the function of homologous recombination DNA repair in malignant pleural effusion (MPE) samples.
abstract: BACKGROUND
  Patients with malignant pleural effusions (MPEs) generally have advanced disease with poor survival and few therapeutic options. Cells within MPEs may be used to stratify patients for targeted therapy. Targeted therapy with poly(ADP ribose) polymerase inhibitors (PARPi) depends on identifying homologous recombination DNA repair (HRR)-defective cancer cells. We aimed to determine the feasibility of assaying HRR status in MPE cells.
  
  
  METHODS
  A total of 15 MPE samples were collected from consenting patients with non-small-cell lung cancer (NSCLC), mesothelioma and ovarian and breast cancer. Primary cultures were confirmed as epithelial by pancytokeratin, and HRR status was determined by the detection of γH2AX and RAD51 foci following a 24-h exposure to rucaparib, by immunofluorescence microscopy. Massively parallel next-generation sequencing of DNA repair genes was performed on cultured MPE cells.
  
  
  RESULTS
  From 15 MPE samples, 13 cultures were successfully established, with HRR function successfully determined in 12 cultures. Four samples - three NSCLC and one mesothelioma - were HRR defective and eight samples - one NSCLC, one mesothelioma, one sarcomatoid, one breast and four ovarian cancers - were HRR functional. No mutations in DNA repair genes were associated with HRR status, but there was probable loss of heterozygosity of FANCG, RPA1 and PARP1.
  
  
  CONCLUSIONS
  HRR function can be successfully detected in MPE cells demonstrating the potential to stratify patients for targeted therapy with PARPi.
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Patterson
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Sutton
authors.affiliation: Royal Victoria Infirmary, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
authors.forename: I
authors.initials: I
authors.lastname: Forrest
authors.affiliation: Royal Victoria Infirmary, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
authors.forename: R
authors.initials: R
authors.lastname: Sharrock
authors.affiliation: Royal Victoria Infirmary, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4LP, UK.
authors.forename: M
authors.initials: M
authors.lastname: Lane
authors.affiliation: 1] Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK [2] The Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead Foundation Trust, Gateshead NE9 6SX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kaufmann
authors.affiliation: 1] Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK [2] The Northern Gynaecological Oncology Centre, Queen Elizabeth Hospital, Gateshead Foundation Trust, Gateshead NE9 6SX, UK.
authors.forename: R
authors.initials: R
authors.lastname: O'Donnell
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Edmondson
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: B T
authors.initials: BT
authors.lastname: Wilson
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Curtin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000235:genetics* / Q000473:pathology; D059767:Recombinational DNA Repair