PMID- 29700339
OWN - NLM
STAT- MEDLINE
DCOM- 20191014
LR  - 20191014
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Apr 26
TI  - Mutational profiling can identify laryngeal dysplasia at risk of progression to 
      invasive carcinoma.
PG  - 6613
LID - 10.1038/s41598-018-24780-7 [doi]
LID - 6613
AB  - Early diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of 
      dysplasia could greatly improve the outcome of affected patients. For the first 
      time we compared the mutational landscape of non-progressing dysplasia (NPD; 
      n = 42) with progressing dysplasia (PD; n = 24), along with patient-matched LSCC 
      biopsies; a total of 90 samples. Using targeted next-generation sequencing 
      identified non-synonymous mutations in six genes (PIK3CA, FGFR3, TP53, JAK3, MET, 
      FBXW7), and mutations were validated by Sanger sequencing and/or qPCR. Analysis 
      was extended in silico to 530 head and neck (HNSCC) cases using TCGA data. 
      Mutations in PIK3CA and FGFR3 were detected in PD and LSCC cases, as well as 
      other HNSCC cases, but absent in NPD cases. In contrast, mutations in JAK3, MET 
      and FBXW7 were found in NPD cases but not PD, LSCC or other HNSCC cases. TP53 was 
      the most frequently mutated gene in both PD and NPD cases. With the exception of 
      R248W, mutations were mutually exclusive. Moreover, five of seven PD mutations 
      were located in motif H2 of p53, whereas none of the NPD mutations were. In 
      summary, we propose that the mutational profile of laryngeal dysplasia has 
      utility for the early detection of patients at risk of progression.
FAU - Manterola, Lorea
AU  - Manterola L
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Aguirre, Pablo
AU  - Aguirre P
AD  - Department of Pathology, Donostia University Hospital, San Sebastian, Gipuzkoa, 
      Spain.
FAU - Larrea, Erika
AU  - Larrea E
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Arestin, Maria
AU  - Arestin M
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Gaafar, Ayman
AU  - Gaafar A
AD  - Department of Pathology, Cruces University Hospital, Barakaldo, Bizkaia, Spain.
FAU - Elorriaga, Kepa
AU  - Elorriaga K
AD  - Department of Pathology, Onkologikoa, San Sebastian, Gipuzkoa, Spain.
FAU - Goicoechea, Ibai
AU  - Goicoechea I
AUID- ORCID: 0000-0002-5329-2225
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Armesto, Maria
AU  - Armesto M
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Fernandez-Mercado, Marta
AU  - Fernandez-Mercado M
AUID- ORCID: 0000-0003-3458-9231
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Zabalza, Ignacio
AU  - Zabalza I
AD  - Department of Pathology, Galdakao-Usansolo Hospital, Galdakao, Bizkaia, Spain.
FAU - Lopez-Duque, Juan Carlos
AU  - Lopez-Duque JC
AD  - Department of Pathology, Basurto University Hospital, Bilbao, Bizkaia, Spain.
FAU - Larruskain, Ekhine
AU  - Larruskain E
AD  - Department of Otolaryngology, Donostia University Hospital, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Sistiaga, Jon Alexander
AU  - Sistiaga JA
AD  - Department of Otolaryngology, Donostia University Hospital, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Landa, Mikel
AU  - Landa M
AD  - Department of Otolaryngology, Donostia University Hospital, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Zabala, Aitor
AU  - Zabala A
AD  - Department of Otolaryngology, Basurto University Hospital, Bilbao, Bizkaia, 
      Spain.
FAU - Santaolalla, Francisco
AU  - Santaolalla F
AD  - Department of Otolaryngology, Basurto University Hospital, Bilbao, Bizkaia, 
      Spain.
FAU - Municio, Jose Antonio
AU  - Municio JA
AD  - Department of Otolaryngology, Cruces University Hospital, Barakaldo, Bizkaia, 
      Spain.
FAU - Ispizua, Angel
AU  - Ispizua A
AD  - Department of Otolaryngology, Donostia University Hospital, San Sebastian, 
      Gipuzkoa, Spain.
FAU - Garcia-Pedrero, Juana Maria
AU  - Garcia-Pedrero JM
AD  - Department of Otolaryngology, Hospital Universitario Central de Asturias and 
      Instituto Universitario de Oncologia del Principado de Asturias, University of 
      Oviedo, CIBERONC, Oviedo, Asturias, Spain.
FAU - Rodrigo, Juan Pablo
AU  - Rodrigo JP
AUID- ORCID: 0000-0003-3063-0890
AD  - Department of Otolaryngology, Hospital Universitario Central de Asturias and 
      Instituto Universitario de Oncologia del Principado de Asturias, University of 
      Oviedo, CIBERONC, Oviedo, Asturias, Spain.
FAU - Lawrie, Charles Henderson
AU  - Lawrie CH
AD  - Molecular Oncology Group, Biodonostia Research Institute, San Sebastian, 
      Gipuzkoa, Spain. charles.lawrie@biodonostia.org.
AD  - Radcliffe Department of Medicine, University of Oxford, Oxford, UK. 
      charles.lawrie@biodonostia.org.
AD  - IKERBASQUE, Basque Foundation for Science, Bilbao, Bizkaia, Spain. 
      charles.lawrie@biodonostia.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180426
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Amino Acid Substitution
MH  - Biomarkers, Tumor
MH  - Computational Biology/methods
MH  - DNA Mutational Analysis
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Profiling
MH  - *Genetic Predisposition to Disease
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Laryngeal Neoplasms/*genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Grading
MH  - Neoplasm Invasiveness
MH  - Neoplasm Staging
MH  - Precancerous Conditions/*genetics/*pathology
MH  - Reproducibility of Results
MH  - Risk Assessment
MH  - Risk Factors
PMC - PMC5919930
COIS- The authors declare no competing interests.
EDAT- 2018/04/28 06:00
MHDA- 2019/10/15 06:00
PMCR- 2018/04/26
CRDT- 2018/04/28 06:00
PHST- 2017/11/03 00:00 [received]
PHST- 2018/04/10 00:00 [accepted]
PHST- 2018/04/28 06:00 [entrez]
PHST- 2018/04/28 06:00 [pubmed]
PHST- 2019/10/15 06:00 [medline]
PHST- 2018/04/26 00:00 [pmc-release]
AID - 10.1038/s41598-018-24780-7 [pii]
AID - 24780 [pii]
AID - 10.1038/s41598-018-24780-7 [doi]
PST - epublish
SO  - Sci Rep. 2018 Apr 26;8(1):6613. doi: 10.1038/s41598-018-24780-7.