PMID- 34638515
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211016
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 19
DP  - 2021 Oct 8
TI  - Methylation Drivers and Prognostic Implications in Sinonasal Poorly 
      Differentiated Carcinomas.
LID - 10.3390/cancers13195030 [doi]
LID - 5030
AB  - BACKGROUND: Poorly differentiated sinonasal carcinomas (PDSNCs) are rare and 
      aggressive malignancies, which include squamous cell carcinoma (SCC), sinonasal 
      undifferentiated carcinoma (SNUC), and neuroendocrine carcinomas (NEC). Several 
      epigenetic markers have been suggested to support the histopathological 
      classification, predict prognosis, and guide therapeutic decision. Indeed, 
      molecularly distinct subtypes of sinonasal carcinomas, including SMARCB1-INI1 or 
      SMARCA4 deficient sinonasal carcinoma, isocitrate dehydrogenase (IDH)-mutant 
      SNUC, ARID1A mutant PDSNCs, and NUT carcinomas, have recently been proposed as 
      separate entities. Identification of aberrant DNA methylation levels associated 
      with these specific epigenetic driver genes could be useful for prognostic and 
      therapeutic purpose. METHODS: Histopathological review and immunohistochemical 
      study was performed on 53 PDSNCs. Molecular analysis included mutational profile 
      by NGS, Sanger sequencing, and MLPA analyses, and global DNA methylation profile 
      using LINE-1 bisulfite-PCR and pyrosequencing analysis. RESULTS: Nine SWI/SNF 
      complex defective cases and five IDH2 p.Arg172x cases were identified. A 
      significant correlation between INI-1 or IDH2 defects and LINE-1 hypermethylation 
      was observed (p = 0.002 and p = 0.032, respectively), which were associated with 
      a worse prognosis (p = 0.007). CONCLUSIONS: Genetic and epigenetic 
      characterization of PDSNCs should be performed to identify distinct prognostic 
      entities, which deserved a tailored clinical treatment.
FAU - Libera, Laura
AU  - Libera L
AUID- ORCID: 0000-0003-2130-6669
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Ottini, Giorgia
AU  - Ottini G
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Sahnane, Nora
AU  - Sahnane N
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Pettenon, Fabiana
AU  - Pettenon F
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Turri-Zanoni, Mario
AU  - Turri-Zanoni M
AUID- ORCID: 0000-0002-3678-9088
AD  - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 
      ASST Sette-Laghi, University of Insubria, 21100 Varese, Italy.
FAU - Lambertoni, Alessia
AU  - Lambertoni A
AD  - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 
      ASST Sette-Laghi, University of Insubria, 21100 Varese, Italy.
FAU - Chiaravalli, Anna Maria
AU  - Chiaravalli AM
AUID- ORCID: 0000-0002-3924-2117
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Leone, Federico
AU  - Leone F
AD  - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 
      ASST Sette-Laghi, University of Insubria, 21100 Varese, Italy.
FAU - Battaglia, Paolo
AU  - Battaglia P
AD  - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 
      ASST Sette-Laghi, University of Insubria, 21100 Varese, Italy.
FAU - Castelnuovo, Paolo
AU  - Castelnuovo P
AD  - Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 
      ASST Sette-Laghi, University of Insubria, 21100 Varese, Italy.
FAU - Uccella, Silvia
AU  - Uccella S
AUID- ORCID: 0000-0002-5714-7295
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Furlan, Daniela
AU  - Furlan D
AUID- ORCID: 0000-0002-5958-5379
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Facco, Carla
AU  - Facco C
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
FAU - Sessa, Fausto
AU  - Sessa F
AD  - Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, 
      University of Insubria, 21100 Varese, Italy.
LA  - eng
PT  - Journal Article
DEP - 20211008
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8507885
OTO - NOTNLM
OT  - CpG island methylator phenotype
OT  - IDH2
OT  - INI1
OT  - LINE-1 methylation
OT  - SMARCB1
OT  - sinonasal neuroendocrine cancer
OT  - undifferentiated cancer
COIS- The authors declare no conflict of interest.
EDAT- 2021/10/14 06:00
MHDA- 2021/10/14 06:01
PMCR- 2021/10/08
CRDT- 2021/10/13 01:02
PHST- 2021/09/13 00:00 [received]
PHST- 2021/09/30 00:00 [revised]
PHST- 2021/10/05 00:00 [accepted]
PHST- 2021/10/13 01:02 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/14 06:01 [medline]
PHST- 2021/10/08 00:00 [pmc-release]
AID - cancers13195030 [pii]
AID - cancers-13-05030 [pii]
AID - 10.3390/cancers13195030 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Oct 8;13(19):5030. doi: 10.3390/cancers13195030.