title: Comprehensive Genomic Profiling of Central Giant Cell Lesions Identifies Clinically Relevant Genomic Alterations.
abstract: OBJECTIVE
  Comprehensive genomic profiling (CGP) can simultaneously detect clinically relevant genomic alterations (CRGAs) in hundreds of cancer-related genes and direct treatment toward patient-specific therapy options for many tumors. This pilot study aimed to use CGP to describe CRGAs present in central giant cell lesions (CGCLs) to characterize any possible underlying genomic drivers of CGCLs.
  
  
  METHODS
  With institutional review board approval, electronic medical records were searched for patients with histologically confirmed CGCLs who underwent biopsy at Mayo Clinic from 2000 through 2014. Clinical characteristics were recorded from the medical records. At least 50 ng of DNA was extracted from formalin-fixed paraffin-embedded archival CGCL specimens by use of hybridization-capture, adaptor ligation-based libraries targeting all exons from 315 cancer-related genes plus select introns from 28 genes commonly rearranged in cancer. Samples were sequenced to high, uniform coverage and assessed for all 4 classes of genomic alterations: base substitutions, small insertions and deletions, rearrangements, and copy number alterations.
  
  
  RESULTS
  Of 8 CGCL specimens, 3 (37.5%) harbored CRGAs, including base substitutions in BRAF, GNAS, and KRAS that are predicted to be oncogenic. In 1 sample, focal high-level amplification of the MITF gene was detected. Rearrangement in the PDGFRB gene was identified in a fourth sample, although the significance of this alteration is uncertain.
  
  
  CONCLUSIONS
  This pilot study shows that a relatively high frequency of CRGAs (37.5%) can be identified in CGCLs by use of CGP. Furthermore, 25% of CGCLs analyzed had somatic mutations predicted to activate the mitogen-activated protein kinase signaling pathway, suggesting it may be a driver of the aggressive behavior of these lesions. On the basis of this study, genomic profiling of a larger cohort of CGCLs to validate these observations, as well as correlate mutations with aggressive versus nonaggressive biological behavior and therapeutic responses, appears warranted.
authors.affiliation: Resident, Division of Oral and Maxillofacial Surgery, Department of Surgery, Mayo Clinic, Rochester, MN. Electronic address: bezak.brett@mayo.edu.
authors.forename: Brett
authors.initials: B
authors.lastname: Bezak
authors.affiliation: Resident, Department of Anatomic/Clinical Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Heidi
authors.initials: H
authors.lastname: Lehrke
authors.affiliation: Associate Medical Director and Senior Pathologist, Foundation Medicine, Cambridge, MA.
authors.forename: Julia
authors.initials: J
authors.lastname: Elvin
authors.affiliation: Senior Scientist, Foundation Medicine, Cambridge, MA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Gay
authors.affiliation: Consultant, Department of Anatomic Pathology, Mayo Clinic, Rochester, MN.
authors.forename: David
authors.initials: D
authors.lastname: Schembri-Wismayer
authors.affiliation: Chair and Consultant, Division of Oral and Maxillofacial Surgery, Department of Surgery, Mayo Clinic, Rochester, MN.
authors.forename: Christopher
authors.initials: C
authors.lastname: Viozzi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D023281:Genomics; D015726:Giant Cells; D006801:Humans; D007573:Jaw Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012189:Retrospective Studies