PMID- 21567085
OWN - NLM
STAT- MEDLINE
DCOM- 20111007
LR  - 20161125
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 39
IP  - 2
DP  - 2011 Aug
TI  - Pyrosequencing-based DNA methylation profiling of Fanconi anemia/BRCA pathway 
      genes in laryngeal squamous cell carcinoma.
PG  - 505-14
LID - 10.3892/ijo.2011.1039 [doi]
AB  - Fanconi anemia (FA) associated genes [FANCA, -B, -C, FANCD1(BRCA2), -D2, -E, -F, 
      -G, -I, -L, -M, FANCN (PALB2), FANCJ(BRIP1) and FA-linked BRCA1] encode proteins 
      of DNA damage response pathways mutated in FA patients. FA is characterized by 
      congenital malformations, chromosomal instability and high cancer susceptibility. 
      FA patients have a 500-700 times higher risk of head and neck squamous cell 
      carcinoma (HNSCC) compared to the non-FA population. As DNA methylation comprises 
      one of the known gene inactivation mechanisms in cancer we have investigated the 
      methylation status of 13 FA and one FA-linked gene in order to assess the role of 
      FA in sporadic laryngeal squamous cell carcinoma (LSCC) tumor samples. Thirteen 
      laryngeal squamous carcinoma cell lines (UT-SCC) and 64 primary laryngeal 
      carcinoma cases were analyzed by bisulfite pyrosequencing. DNA from buccal swabs 
      of 10 healthy volunteers was used as a control group. Promoter regions of FANCA, 
      BRCA1 and BRCA2 displayed recurrent alterations in the methylation levels in 
      cancer samples as compared to buccal swabs controls. For FANCA, hypomethylation 
      was observed in 11/13 cell lines (p<0.0003) and all 64 primary larynx samples 
      (p<0.001) compared to buccal swabs. For BRCA1, 4/13 cell lines (p=0.04) and 3/58 
      primary laryngeal cases (p=0.22) showed hypomethylation. In BRCA2, all 13 cell 
      lines (p<0.0001) 4/63 primary LSCC (p<0.01) showed hypermethylation as compared 
      to controls. In conclusion, we show recurrent alterations of DNA methylation 
      levels in three Fanconi anemia genes which might contribute to the pathogenesis 
      of LSCC.
FAU - Szaumkessel, Marcin
AU  - Szaumkessel M
AD  - Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus 
      Kiel/Christian-Albrechts, University Kiel, D-24105 Kiel, Germany. 
      marcinsz@man.poznan.pl
FAU - Richter, Julia
AU  - Richter J
FAU - Giefing, Maciej
AU  - Giefing M
FAU - Jarmuz, Malgorzata
AU  - Jarmuz M
FAU - Kiwerska, Katarzyna
AU  - Kiwerska K
FAU - Tonnies, Holger
AU  - Tonnies H
FAU - Grenman, Reidar
AU  - Grenman R
FAU - Heidemann, Simone
AU  - Heidemann S
FAU - Szyfter, Krzysztof
AU  - Szyfter K
FAU - Siebert, Reiner
AU  - Siebert R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110511
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Fanconi Anemia Complementation Group Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Cell Line, Tumor
MH  - *DNA Methylation
MH  - *Epigenomics
MH  - Fanconi Anemia Complementation Group Proteins/*genetics
MH  - Female
MH  - Humans
MH  - Laryngeal Neoplasms/*genetics
MH  - Male
MH  - Neoplasms, Squamous Cell/*genetics
MH  - Promoter Regions, Genetic
MH  - Ubiquitin-Protein Ligases/*genetics
EDAT- 2011/05/14 06:00
MHDA- 2011/10/08 06:00
CRDT- 2011/05/14 06:00
PHST- 2011/02/11 00:00 [received]
PHST- 2011/04/07 00:00 [accepted]
PHST- 2011/05/14 06:00 [entrez]
PHST- 2011/05/14 06:00 [pubmed]
PHST- 2011/10/08 06:00 [medline]
AID - 10.3892/ijo.2011.1039 [doi]
PST - ppublish
SO  - Int J Oncol. 2011 Aug;39(2):505-14. doi: 10.3892/ijo.2011.1039. Epub 2011 May 11.