PMID- 19047905
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20211020
IS  - 1538-7151 (Electronic)
IS  - 0277-1691 (Print)
IS  - 0277-1691 (Linking)
VI  - 28
IP  - 1
DP  - 2009 Jan
TI  - DNA hypermethylation profiles in squamous cell carcinoma of the vulva.
PG  - 63-75
LID - 10.1097/PGP.0b013e31817d9c61 [doi]
AB  - Gene silencing through promoter hypermethylation is a growing concept in the 
      development of human cancers. In this study, we examined the contribution of 
      aberrant methylation of promoter regions in methylation-prone tumor suppressors 
      to the pathogenesis of vulvar cancer. Thirteen cell lines from 12 patients with 
      squamous cell carcinoma of the vulva were evaluated for aberrant methylation 
      status and gene copy number alterations, concomitantly, using the 
      methylation-specific multiplex ligation-dependent probe amplification assay. Of 
      the 22 tumor suppressor genes examined, aberrant methylation was observed for 9 
      genes: tumor protein p73 (TP73), fragile histidine triad (FHIT), von 
      Hippel-Lindau (VHL), adenomatosis polyposis coli (APC), estrogen receptor 1 
      (ESR1), cyclin-dependent kinase inhibitor 2B (CDKN2B), death-associated protein 
      kinase 1 (DAPK1), glutathione S-transferase pi (GSTP1), and immunoglobin 
      superfamily, member 4 (IGSF4). The most frequently methylated genes included TP73 
      in 9 of 13 cell lines, and IGSF4, DAPK1, and FHIT in 3 of 13 cell lines. 
      Methylation-specific polymerase chain reaction was performed for TP73 and FHIT to 
      confirm aberrant methylation by methylation-specific multiplex ligation-dependent 
      probe amplification. In the context of gene copy number and methylation status, 
      both copies of the TP73 gene were hypermethylated. Loss or decreased mRNA 
      expression of TP73 and IGSF4 by reverse transcription polymerase chain reaction 
      confirmed aberrant methylation. Frequent genetic alterations of loss and gain of 
      gene copy number included gain of GSTP1 and multiple endocrine neoplasia type 1 
      (MEN1), and loss of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) 
      and IGSF4 in over 50% of the squamous cell carcinoma of the vulva cell lines. 
      These findings underscore the contribution of both genetic and epigenetic events 
      to the underlying pathogenesis of squamous cell carcinoma of the vulva.
FAU - Stephen, Josena K
AU  - Stephen JK
AD  - Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, 
      Detroit, Michigan 48202, USA.
FAU - Chen, Kang Mei
AU  - Chen KM
FAU - Raitanen, Misa
AU  - Raitanen M
FAU - Grenman, Seija
AU  - Grenman S
FAU - Worsham, Maria J
AU  - Worsham MJ
LA  - eng
GR  - R01 DE015990/DE/NIDCR NIH HHS/United States
GR  - R01 DE015990-05/DE/NIDCR NIH HHS/United States
GR  - DE 15990/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Int J Gynecol Pathol
JT  - International journal of gynecological pathology : official journal of the 
      International Society of Gynecological Pathologists
JID - 8214845
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/*genetics
MH  - *DNA Methylation
MH  - Epigenesis, Genetic
MH  - Female
MH  - Gene Dosage
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Middle Aged
MH  - Promoter Regions, Genetic/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vulvar Neoplasms/*genetics
PMC - PMC2605778
MID - NIHMS52427
EDAT- 2008/12/03 09:00
MHDA- 2009/03/04 09:00
PMCR- 2009/01/01
CRDT- 2008/12/03 09:00
PHST- 2008/12/03 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
PHST- 2008/12/03 09:00 [entrez]
PHST- 2009/01/01 00:00 [pmc-release]
AID - 10.1097/PGP.0b013e31817d9c61 [doi]
PST - ppublish
SO  - Int J Gynecol Pathol. 2009 Jan;28(1):63-75. doi: 10.1097/PGP.0b013e31817d9c61.