PMID- 30094098
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 8
IP  - 7
DP  - 2018
TI  - Downregulation of CEACAM6 gene expression in laryngeal squamous cell carcinoma is 
      an effect of DNA hypermethylation and correlates with disease progression.
PG  - 1249-1261
AB  - We have turned our attention to CEACAM6 gene, already described as deregulated in 
      various types of cancer. By using the expression microarrays performed on the set 
      of 16 laryngeal squamous cell carcinoma (LSCC) samples: 11 cell lines and 5 
      primary tumors we have shown downregulation of CEACAM6 gene as compared to non 
      cancer controls from head and neck region. CEACAM6 gene downregulation, further 
      confirmed by quantitative PCR on 25 LSCC cell lines, was observed in cell lines 
      derived from recurrent tumors in comparison to controls. A significant gene 
      downregulation was observed in cell lines derived from advanced, high grade 
      tumors in comparison to controls. Intrigued by the recurrent transcriptional loss 
      of CEACAM6 we searched for the mechanism potentially responsible for its 
      downregulation and hence we analyzed DNA copy number changes (a-CGH), promoter 
      DNA methylation status and occurrence of gene mutations (in silico). Neither the 
      analysis of gene copy number, nor the mutation screen has shown recurrent 
      deletions or mutations, that could contribute to the observed downregulation of 
      the gene. However, by using bisulfite pyrosequencing, we have shown DNA 
      hypermethylation (mean DNA methylation > 78%) of CEACAM6 promoter region in 9/25 
      (36%) LSCC cell lines. Importantly, the 5-aza-2-deoxycytidine-induced inhibition 
      of DNA methylation resulted in restoration of CEACAM6 expression in the two LSCC 
      cell lines on mRNA level. In summary, we have shown that recurrent downregulation 
      of CEACAM6 in LSCC is dependent on the gene's promoter DNA methylation and is 
      observed predominantly in large, poorly differentiated tumors and recurrences.
FAU - Bednarek, Kinga
AU  - Bednarek K
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Kostrzewska-Poczekaj, Magdalena
AU  - Kostrzewska-Poczekaj M
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Szaumkessel, Marcin
AU  - Szaumkessel M
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Kiwerska, Katarzyna
AU  - Kiwerska K
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
AD  - Department of Tumor Pathology, Greater Poland Cancer Center Poznan, Poland.
FAU - Paczkowska, Julia
AU  - Paczkowska J
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Byzia, Ewa
AU  - Byzia E
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Ustaszewski, Adam
AU  - Ustaszewski A
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Janiszewska, Joanna
AU  - Janiszewska J
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Bartochowska, Anna
AU  - Bartochowska A
AD  - Department of Otolaryngology and Laryngological Oncology, Poznan University of 
      Medical Sciences Poznan, Poland.
FAU - Grenman, Reidar
AU  - Grenman R
AD  - Department of Otorhinolaryngology-Head and Neck Surgery and Department of Medical 
      Biochemistry, Turku University Hospital and University of Turku Turku, Finland.
FAU - Wierzbicka, Malgorzata
AU  - Wierzbicka M
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
AD  - Department of Otolaryngology and Laryngological Oncology, Poznan University of 
      Medical Sciences Poznan, Poland.
FAU - Szyfter, Krzysztof
AU  - Szyfter K
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
FAU - Giefing, Maciej
AU  - Giefing M
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
AD  - Department of Otolaryngology and Laryngological Oncology, Poznan University of 
      Medical Sciences Poznan, Poland.
FAU - Jarmuz-Szymczak, Malgorzata
AU  - Jarmuz-Szymczak M
AD  - Institute of Human Genetics, Polish Academy of Sciences Poznan, Poland.
AD  - Department of Hematology and Bone Marrow Transplantation, Poznan University of 
      Medical Sciences Poznan, Poland.
LA  - eng
PT  - Journal Article
DEP - 20180701
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC6079150
OTO - NOTNLM
OT  - CEACAM6
OT  - DNA methylation
OT  - Laryngeal squamous cell carcinoma (LSCC)
OT  - head and neck squamous cell carcinoma (HNSCC)
OT  - tumor suppressor gene
COIS- None.
EDAT- 2018/08/11 06:00
MHDA- 2018/08/11 06:01
PMCR- 2018/07/01
CRDT- 2018/08/11 06:00
PHST- 2018/05/17 00:00 [received]
PHST- 2018/05/27 00:00 [accepted]
PHST- 2018/08/11 06:00 [entrez]
PHST- 2018/08/11 06:00 [pubmed]
PHST- 2018/08/11 06:01 [medline]
PHST- 2018/07/01 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2018 Jul 1;8(7):1249-1261. eCollection 2018.