title: TERT promoter mutations and BRAF mutations are rare in sporadic, and TERT promoter mutations are absent in NF1-related malignant peripheral nerve sheath tumors.
abstract: Hot spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in tumors of neuroectodermal origin such as melanoma and glioma. Many of these tumors are of neuroectodermal or ectomesenchymal origin which is suggestive of TERT promoter mutations playing a role in the development of malignant peripheral nerve sheath tumors (MPNSTs). In melanoma a correlation has been suggested between the occurrence of TERT promoter mutations and v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) mutations. We investigated TERT promoter and BRAF mutation frequency in respectively 94 and 86 consecutive MPNST cases from our institute. TERT promoter mutation analysis on DNA from formalin-fixed, paraffin-embedded specimens was performed by SNaPshot analysis. Sequence analysis of BRAF was performed by bidirectional DNA sequencing. We identified TERT C228T or C250T promoter mutations in 10 % (9/94) and BRAF V600E mutations in 3 % (3/86) of MPNSTs. All TERT promoter- and BRAF mutations occurred in NF1 unrelated tumors. One co-occurrence of a TERT promoter- and a BRAF mutation was observed. In comparison with other neuroectodermal derived malignant neoplasms, TERT promoter mutations occur at relatively low frequency in MPNSTs. The observation of TERT promotor and BRAF mutations in sporadic MPNSTs and the absence of TERT promotor and rarity of BRAF mutations in NF1 related tumors may imply an alternative genetic route of tumor progression in both patient groups.
authors.affiliation: Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, PO-Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Hendrikus J
authors.initials: HJ
authors.lastname: Dubbink
authors.forename: Hannah
authors.initials: H
authors.lastname: Bakels
authors.forename: Edward
authors.initials: E
authors.lastname: Post
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: Robert M
authors.initials: RM
authors.lastname: Verdijk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C509186:TERT protein, human; D019098:Telomerase