title: ROS1 copy number alterations are frequent in non-small cell lung cancer.
abstract: OBJECTIVE
  We aimed to determine the prevalence and partners of ROS1 rearrangements, to explore the correlation between FISH and IHC assays, and to investigate clinical implications of ROS1 copy number alterations (CNAs).
  
  
  METHODS
  A total of 314 NSCLC patients were screened using ROS1 FISH break-apart probes. Of these, 47 surgical tumors were included in TMAs to analyze ROS1 heterogeneity assessed either by FISH and IHC, and chromosome 6 aneusomy. To characterize ROS1 partners, probes for CD74, EZR, SLC34A2 and SDC3 genes were developed. ROS1 positive FISH cases were screened also by IHC.
  
  
  RESULTS
  Five patients were ROS1 positive (1.8%). We identified two known fusion partners in three patients: CD74 and SLC34A2. Four out of five ROS1 rearranged patients were female, never smokers and with adenocarcinoma histology. Rearranged cases were also positive by IHC as well. According to ROS1 CNAs, we found a prevalence of 37.8% gains/amplifications and 25.1% deletions.
  
  
  CONCLUSIONS
  This study point out the high prevalence of ROS1 CNAs in a large series of NSCLC. ROS1 gains, amplifications and deletions, most of them due to chromosome 6 polysomy or monosomy, were heterogeneous within a tumor and had no impact on overall survival.
authors.affiliation: Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Programa de Recerca en Càncer, IMIM (Institut Hospital del Mar de Investigacions Mèdiques), Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Clavé
authors.affiliation: Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gimeno
authors.affiliation: Servei de Anatomia Patològica, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Muñoz-Mármol
authors.affiliation: Servei de Oncologia Mèdica, Hospital del Mar, Barcelona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Vidal
authors.affiliation: Servei de Oncologia Mèdica, ICMHO, Hospital Clinic Barcelona, Barcelona, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Reguart
authors.affiliation: Departament de Oncologia Mèdica, Institut Català de Oncologia (ICO), Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Carcereny
authors.affiliation: Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Pijuan
authors.affiliation: Programa de Recerca en Càncer, IMIM (Institut Hospital del Mar de Investigacions Mèdiques), Barcelona, Spain.|Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Menéndez
authors.affiliation: Servei de Oncologia Mèdica, Hospital del Mar, Barcelona, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Taus
authors.affiliation: Servei de Anatomia Patològica, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: José Luís
authors.initials: JL
authors.lastname: Mate
authors.affiliation: Servei de Patologia, Hospital del Mar, Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano
authors.affiliation: Programa de Recerca en Càncer, IMIM (Institut Hospital del Mar de Investigacions Mèdiques), Barcelona, Spain.|Servei de Oncologia Mèdica, Hospital del Mar, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Programa de Recerca en Càncer, IMIM (Institut Hospital del Mar de Investigacions Mèdiques), Barcelona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.affiliation: Programa de Recerca en Càncer, IMIM (Institut Hospital del Mar de Investigacions Mèdiques), Barcelona, Spain.|Cancer Sciences Unit, University of Southampton. Southampton, United Kingdom.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
authors.affiliation: Laboratori de Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain.|Programa de Recerca en Càncer, IMIM (Institut Hospital del Mar de Investigacions Mèdiques), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: FISH; IHC; ROS1; copy number alterations; heterogeneity