TY - JOUR
T1 - Fragile genes as biomarkers
T2 - Epigenetic control of WWOX and FHIT in lung, breast and bladder cancer
AU - Iliopoulos, Dimitrios
AU - Guler, Gulnur
AU - Han, Shuang Yin
AU - Johnston, Danika
AU - Druck, Teresa
AU - McCorkell, Kelly A.
AU - Palazzo, Juan
AU - McCue, Peter A.
AU - Baffa, Raffaele
AU - Huebner, Kay
PY - 2005/1/24
Y1 - 2005/1/24
N2 - This study aimed to (a) determine if DNA methylation is a mechanism of WWOX (WW domain containing oxidoreductase) and FHIT (fragile histidine triad) inactivation in lung, breast and bladder cancers; (b) examine distinct methylation patterns in neoplastic and adjacent tissues and (c) seek correlation of methylation patterns with disease status. Protein expression was detected by immunohistochemistry, and methylation status by methylation-specific PCR (MSP) and sequencing, in lung squamous cell carcinomas and adjacent tissues, invasive breast carcinomas, adjacent tissues and normal mammary tissues and bladder transitional cell carcinomas. Wwox and Fhit expression was reduced in cancers in association with hypermethylation. Differential patterns of WWOX and FHIT methylation were observed in neoplastic vs adjacent non-neoplastic tissues, suggesting that targeted MSP amplification could be useful in following treatment or prevention protocols. WWOX promoter MSP differentiates DNA of lung cancer from DNA of adjacent lung tissue. WWOX and FHIT promoter methylation is detected in tissue adjacent to breast cancer and WWOX exon 1 MSP distinguishes breast cancer DNA from DNA of adjacent and normal tissue. Differential methylation in cancerous vs adjacent tissues suggests that WWOX and FHIT hypermethylation analyses could enrich a panel of DNA methylation markers.
AB - This study aimed to (a) determine if DNA methylation is a mechanism of WWOX (WW domain containing oxidoreductase) and FHIT (fragile histidine triad) inactivation in lung, breast and bladder cancers; (b) examine distinct methylation patterns in neoplastic and adjacent tissues and (c) seek correlation of methylation patterns with disease status. Protein expression was detected by immunohistochemistry, and methylation status by methylation-specific PCR (MSP) and sequencing, in lung squamous cell carcinomas and adjacent tissues, invasive breast carcinomas, adjacent tissues and normal mammary tissues and bladder transitional cell carcinomas. Wwox and Fhit expression was reduced in cancers in association with hypermethylation. Differential patterns of WWOX and FHIT methylation were observed in neoplastic vs adjacent non-neoplastic tissues, suggesting that targeted MSP amplification could be useful in following treatment or prevention protocols. WWOX promoter MSP differentiates DNA of lung cancer from DNA of adjacent lung tissue. WWOX and FHIT promoter methylation is detected in tissue adjacent to breast cancer and WWOX exon 1 MSP distinguishes breast cancer DNA from DNA of adjacent and normal tissue. Differential methylation in cancerous vs adjacent tissues suggests that WWOX and FHIT hypermethylation analyses could enrich a panel of DNA methylation markers.
KW - CpG island methylation
KW - FHIT
KW - Methylation patterns
KW - Molecular markers
KW - WWOX
UR - http://www.scopus.com/inward/record.url?scp=20144372911&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208398
DO - 10.1038/sj.onc.1208398
M3 - Article
C2 - 15674328
AN - SCOPUS:20144372911
SN - 0950-9232
VL - 24
SP - 1625
EP - 1633
JO - Oncogene
JF - Oncogene
IS - 9
ER -
