title: Increased copy number at 3p14 in breast cancer.
abstract: BACKGROUND
  The present study was conducted to investigate if chromosome band 3p14 is of any pathogenic significance in the malignant process of breast cancer. Genetic studies have implicated a tumour suppressor gene on chromosome arm 3p and we have proposed LRIG1 at 3p14 as a candidate tumour suppressor. The LRIG1 gene encodes an integral membrane protein that counteracts signalling by receptor tyrosine kinases belonging to the ERBB family. LRIG1 mRNA and protein are expressed in many tissues, including breast tissue.
  
  
  METHODS
  In the present report we analysed the LRIG1 gene by fluorescence in situ hybridisation (FISH), LRIG1 mRNA by quantitative RT-PCR, and LRIG1 protein by western blot analysis. Two tumour series were analysed; one series consisted of 19 tumour samples collected between 1987 and 1995 and the other series consisted of 9 tumour samples with corresponding non-neoplastic breast tissues collected consecutively.
  
  
  RESULTS
  The LRIG1 gene showed increased copy number in 11 out of 28 tumours (39%) and only one tumour showed a deletion at this locus. Increased LRIG1 copy number was associated with increased levels of LRIG1 mRNA (two of three tumours) and protein (four of four tumours) in the tumours compared to matched non-neoplastic breast tissue, as assessed by RT-PCR and western blot analysis.
  
  
  CONCLUSIONS
  The molecular function of LRIG1 as a negative regulator of ERBB receptors questions the biological significance of increased LRIG1 copy number in breast cancer. We propose that a common, but hitherto unrecognised, breast cancer linked gene is located within an amplicon containing the LRIG1 locus at 3p14.3.
authors.affiliation: Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. ingrid.ljuslinder@onkologi.umu.se
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ljuslinder
authors.forename: Beatrice
authors.initials: B
authors.lastname: Malmer
authors.forename: Irina
authors.initials: I
authors.lastname: Golovleva
authors.forename: Marcus
authors.initials: M
authors.lastname: Thomasson
authors.forename: Kjell
authors.initials: K
authors.lastname: Grankvist
authors.forename: Thomas
authors.initials: T
authors.lastname: Höckenström
authors.forename: Stefan
authors.initials: S
authors.lastname: Emdin
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Jonsson
authors.forename: Håkan
authors.initials: H
authors.lastname: Hedman
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D002871:Chromosome Banding; D002893:Chromosomes, Human, Pair 3; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008562:Membrane Glycoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D066246:ErbB Receptors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; C484445:LRIG1 protein, human