title: Does PTEN gene mutation play any role in Li-Fraumeni syndrome.
abstract: BACKGROUND
  Li-Fraumeni syndrome (LFS) is one of the most serious hereditary cancer syndromes with a high risk of malignancy in childhood. This syndrome is an autosomal dominant cancer predisposing syndrome due to a germline mutation in the TP53 tumor suppressor gene.
  
  
  METHODS
  In this study, a representative family case of Li-Fraumeni syndrome is described. The proband of this family was a 43-year-old male who had osteosarcoma of the mandible and a positive family history of cancer. His mother died at the age of 29 of brain cancer; his sister died at the age of 18 of breast cancer; his brother died at the age of 36 of liver cancer; and another sister of his died at the age of 16 of leukemia. Complete sequence analysis of the TP53 and PTEN genes was performed in this family. We used standard diagnostic tools such as sequencing and multiplex ligation-dependent probe amplification (MLPA) to analyze these two genes in this family. The exons and flanking exon-intron junctions of the TP53 and PTEN genes were sequenced.
  
  
  RESULTS
  We detected a germline mutation in the TP53 gene in this family that was previously reported as somatic mutation in LFS in the catalogue of somatic mutations in cancer (COSMIC). In addition, according to the International Agency for Research of Cancer (IARC) database, a 19-year-old male patient with sarcoma was recently reported to have this germline mutation. We also found two new IVS variations in the PTEN gene, one of which can be a suggestive evidence of an effect on the splicing of PTEN.
  
  
  CONCLUSIONS
  Genomic modifications for tumor risk and genotype-phenotype correlations in LFS are still to be identified. We believe every new finding in this area can provide new insights into the pathogenesis and progression of Li-Fraumeni syndrome.
authors: PhD, Assistant Professor, Department of Medical Genetics & Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. akouchekian.m@iums.ac.ir.
authors: Mansoureh
authors: M
authors: Akouchekian
authors: MD, PhD, Associate Professor, Department of Oncology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. hematti@med.mui.ac.ir.
authors: Simin
authors: S
authors: Hemati
authors: MSc, PhD student, Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. davoodjafari1@yahoo.com.
authors: Davood
authors: D
authors: Jafari
authors: PhD, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. jalilian_n@razi.tums.ac.ir.
authors: Nazanin
authors: N
authors: Jalilian
authors: MSc, Medical Genetics Department, Special Medical Center, Tehran, Iran. m_dehghanmanshadi@yahoo.com.
authors: Masoumeh
authors: M
authors: Dehghan Manshadi
keywords: Germline Mutation; Li-Fraumeni Syndrome; PTEN Gene