TY - JOUR
T1 - CpG island methylation and expression of tumour-associated genes in lung carcinoma
AU - Dammann, Reinhard
AU - Strunnikova, Maria
AU - Schagdarsurengin, Undraga
AU - Rastetter, Matthias
AU - Papritz, Mirko
AU - Hattenhorst, Uwe E.
AU - Hofmann, Hans Stefan
AU - Silber, Rolf Edgar
AU - Burdach, Stefan
AU - Hansen, Gesine
N1 - Funding Information:
We are grateful to Prof. Heidi Foth of the Institute for Environmental Toxicology, University Halle for the possibility to perform real-time PCR. We thank Christel Trümpler for technical assistance. This work was supported by BMBF (FKZ 01ZZ0104), Land Sachsen-Anhalt and DFG (DA 552-1) Grants to Reinhard Dammann and DFG (SFB 610 TPB1) and Deutsche Krebshilfe (70-2787-Bu3) Grants to Stefan Burdach.
PY - 2005/5
Y1 - 2005/5
N2 - In this study, microarray analysis was used to identify tumour-related genes that were down regulated in lung carcinoma. The promoter sequences of the identified genes were analysed for methylation patterns. In lung cancer cell lines, CpG island methylation was frequently detected for TIMP4 (64%), SOX18 (73%), EGF-like domain 7 (56%), CD105 (71%), SEMA2 (55%), RASSF1A (71%), p16 (56%) SLIT2 (100%) and TIMP3 (29%). Methylation was however rarely observed in cell lines for SLIT3 (18%) and DLC1 (18%). In primary lung tumours, methylation of TIMP4 (94%), SOX18 (100%), EGF-like domain 7 (100%), CD105 (69%), SEMA2 (93%), DLC1 (61%), RASSF1A (44%), p16 (47%), SLIT2 (100%) and TIMP3 (13%) was also detected. Methylation of several CpG islands was frequently found in normal lung tissue of cancer patients and this may have been attributed to epigenetic field defect and/or infiltrating tumour cells. Interestingly, inactivation of RASSF1A and p16 correlated well with an extended smoking habit (P = 0.02), and exposure to asbestos (P = 0.017) or squamous cell carcinoma (P = 0.011), respectively. These results have identified genes whose aberrant promoter methylation could play a crucial role in the malignancy of lung carcinoma.
AB - In this study, microarray analysis was used to identify tumour-related genes that were down regulated in lung carcinoma. The promoter sequences of the identified genes were analysed for methylation patterns. In lung cancer cell lines, CpG island methylation was frequently detected for TIMP4 (64%), SOX18 (73%), EGF-like domain 7 (56%), CD105 (71%), SEMA2 (55%), RASSF1A (71%), p16 (56%) SLIT2 (100%) and TIMP3 (29%). Methylation was however rarely observed in cell lines for SLIT3 (18%) and DLC1 (18%). In primary lung tumours, methylation of TIMP4 (94%), SOX18 (100%), EGF-like domain 7 (100%), CD105 (69%), SEMA2 (93%), DLC1 (61%), RASSF1A (44%), p16 (47%), SLIT2 (100%) and TIMP3 (13%) was also detected. Methylation of several CpG islands was frequently found in normal lung tissue of cancer patients and this may have been attributed to epigenetic field defect and/or infiltrating tumour cells. Interestingly, inactivation of RASSF1A and p16 correlated well with an extended smoking habit (P = 0.02), and exposure to asbestos (P = 0.017) or squamous cell carcinoma (P = 0.011), respectively. These results have identified genes whose aberrant promoter methylation could play a crucial role in the malignancy of lung carcinoma.
KW - Epigenetics
KW - Lung cancer
KW - Methylation
KW - Tumour-suppressor gene
UR - http://www.scopus.com/inward/record.url?scp=21144453099&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2005.02.020
DO - 10.1016/j.ejca.2005.02.020
M3 - Article
C2 - 15911247
AN - SCOPUS:21144453099
SN - 0959-8049
VL - 41
SP - 1223
EP - 1236
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 8
ER -
