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The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.
Ueda, Kaori; Murase, Takayuki; Kawakita, Daisuke; Nagao, Toshitaka; Kusafuka, Kimihide; Nakaguro, Masato; Urano, Makoto; Yamamoto, Hidetaka; Taguchi, Ken-Ichi; Kano, Satoshi; Tada, Yuichiro; Tsukahara, Kiyoaki; Okami, Kenji; Onitsuka, Tetsuro; Fujimoto, Yasushi; Sakurai, Kazuo; Hanai, Nobuhiro; Nagao, Toru; Kawata, Ryo; Hato, Naohito; Nibu, Ken-Ichi; Inagaki, Hiroshi.
Afiliación
  • Ueda K; Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
  • Murase T; Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Kawakita D; Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Nagao T; Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.
  • Kusafuka K; Department of Pathology, Shizuoka General Hospital, Shizuoka, Japan.
  • Nakaguro M; Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
  • Urano M; Department of Diagnostic Pathology, Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan.
  • Yamamoto H; Department of Anatomic Pathology, Graduate of School of Medical Science, Kyushu University, Fukuoka, Japan.
  • Taguchi KI; Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
  • Kano S; Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
  • Tada Y; Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Tokyo, Japan.
  • Tsukahara K; Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Tokyo, Japan.
  • Okami K; Department of Otolaryngology-Head and Neck Surgery, Tokai University School of Medicine, Isehara, Japan.
  • Onitsuka T; Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
  • Fujimoto Y; Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Otolaryngology-Head and Neck Surgery, Aichi Medical University, Nagakute, Japan.
  • Sakurai K; Department of Otorhinolaryngology, Fujita Health University, Okazaki Medical Center, Okazaki, Japan.
  • Hanai N; Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Nagao T; Department of Maxillofacial Surgery, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
  • Kawata R; Department of Otorhinolaryngology-Head and Neck Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
  • Hato N; Department of Otolaryngology, Ehime University School of Medicine, Toon, Japan.
  • Nibu KI; Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
  • Inagaki H; Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address: hinagaki@med.nagoya-cu.ac.jp.
Mod Pathol ; 36(10): 100274, 2023 Oct.
Article en En | MEDLINE | ID: mdl-37423587
ABSTRACT
Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYBNFIB or MYBL1NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYBNFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.
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Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Año: 2023 Tipo del documento: Article