title: Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: increased expression of a CD44 variant isoform after chemotherapy.
abstract: BACKGROUND
  Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome that is commonly associated with a germline mutation in the tumor suppressor gene p53. Loss of p53 results in increased expression of CD44, a cancer stem cell (CSC) marker, which is involved in the scavenging of reactive oxygen species (ROS). Here, we report a change in the expression of a CD44 variant isoform (CD44v8-10) in an 8-year-old female LFS patient with osteosarcoma and atypical liver cancer after chemotherapy.
  
  
  METHODS
  The patient visited a clinic with a chief complaint of chronic pain in a bruise on her right knee. Magnetic resonance imaging (MRI) raised the possibility of a bone malignancy. Biochemical testing also revealed significantly elevated levels of AFP, which strongly suggested the existence of a primary malignancy in the liver. MRI imaging showed the simultaneous development of osteosarcoma and liver cancer, both of which were confirmed upon biopsy. Combined therapy with surgical resection after chemotherapy was successful in this patient. Regardless of the absence of a familial history of hereditary cancer, a germline mutation in p53 was identified (a missense mutation defined as c.722 C>T, p.Ser241Phe). To better understand the cancer progression and response to treatment, immunohistochemical (IHC) analysis of biopsy specimens obtained before and after chemotherapy was performed using a specific antibody against CD44v8-10.
  
  
  CONCLUSIONS
  This case demonstrates the ectopic up-regulation of CD44v8-10 in a biopsy sample obtained after cytotoxic chemotherapy, which confers high levels of oxidative stress on cancer cells. Because the alternative splicing of CD44 is tightly regulated epigenetically, it is possible that micro-environmental stress resulting from chemotherapy caused the ectopic induction of CD44v8-10 in vivo.
authors.affiliation: Division of Gene Regulation, Institute for Advanced Medical Research, KeioUniversity School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 1608582, Japan.
authors.forename: Go J
authors.initials: GJ
authors.lastname: Yoshida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fuchimoto
authors.forename: Tomoo
authors.initials: T
authors.lastname: Osumi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimada
authors.forename: Seiichi
authors.initials: S
authors.lastname: Hosaka
authors.forename: Hideo
authors.initials: H
authors.lastname: Morioka
authors.forename: Makio
authors.initials: M
authors.lastname: Mukai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Masugi
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kuroda
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002648:Child; D005260:Female; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D016864:Li-Fraumeni Syndrome / Q000150:complications* / Q000235:genetics; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D012516:Osteosarcoma / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D018960:Hyaluronan Receptors; D020033:Protein Isoforms