title: Altered Lamin A/C splice variant expression as a possible diagnostic marker in breast cancer.
abstract: BACKGROUND
  Lamin A/C alternative splice variants (Lamin A, Lamin C, Lamin AΔ10 and Lamin AΔ50) have been implicated in cell cycle regulation, DNA replication, transcription regulation, cellular differentiation, apoptosis and aging. In addition, loss of Lamin A/C expression has been observed in several cancers, including breast cancer, and it has been found that Lamin A/C suppression may lead to cancer-like aberrations in nuclear morphology and aneuploidy. Based on these observations, we hypothesized that Lamin A/C transcript variant quantification might be employed for the diagnosis of breast cancer.
  
  
  METHODS
  Newly designed TaqMan qRT-PCR assays for the analysis of Lamin A/C splice variants were validated and their use as biomarkers for the diagnosis of breast cancer was assessed using 16 normal breast tissues and 128 breast adenocarcinomas. In addition, the expression levels of the Lamin A/C transcript variants were measured in samples derived from seven other types of cancer.
  
  
  RESULTS
  We found that the expression level of Lamin C was significantly increased in the breast tumors tested, whereas the expression levels of Lamin A and Lamin AΔ50 were significantly decreased. No significant change in Lamin AΔ10 expression was observed. Our data also indicated that the Lamin C : Lamin A mRNA ratio was increased in all clinical stages of breast cancer. Additionally, we observed increased Lamin C : Lamin A mRNA ratios in liver, lung and thyroid carcinomas and in colon, ovary and prostate adenocarcinomas.
  
  
  CONCLUSIONS
  From our data we conclude that the Lamin C : Lamin A mRNA ratio is increased in breast cancer and that this mRNA ratio may be of diagnostic use in all clinical stages of breast cancer and, possibly, also in liver, lung, thyroid, colon, ovary and prostate cancers.
authors.affiliation: Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. aljadaa@ksau-hs.edu.sa.|King Abdullah International Medical Research Center (KAIMRC), National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. aljadaa@ksau-hs.edu.sa.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Aljada
authors.affiliation: Department of Neurology, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Doria
authors.affiliation: Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.|King Abdullah International Medical Research Center (KAIMRC), National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ayman M
authors.initials: AM
authors.lastname: Saleh
authors.affiliation: Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Shahad H
authors.initials: SH
authors.lastname: Al-Matar
authors.affiliation: Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Sarah
authors.initials: S
authors.lastname: AlGabbani
authors.affiliation: King Abdullah International Medical Research Center (KAIMRC), National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Heba Bani
authors.initials: HB
authors.lastname: Shamsa
authors.affiliation: Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al-Bawab
authors.affiliation: Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Altayeb Abdalla
authors.initials: AA
authors.lastname: Ahmed
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D034904:Lamin Type A; D012333:RNA, Messenger; C440308:lamin C
keywords: Breast cancer; Lamin A/C; Metastasis; Progerin; Tumor marker