TY - JOUR
T1 - Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer
AU - Ito, Masao
AU - Ito, Genshi
AU - Kondo, Masashi
AU - Uchiyama, Mika
AU - Fukui, Takayuki
AU - Mori, Shoichi
AU - Yoshioka, Hiromu
AU - Ueda, Yuichi
AU - Shimokata, Kaoru
AU - Sekido, Yoshitaka
N1 - Funding Information:
This research was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. We would like to acknowledge Dr Koichi Fujita, Dr Norio Mukoyama, Dr Naohito Sato, and Dr Norio Maeda for the surgical specimens and Ms Hiroko Kako for technical support.
PY - 2005/7/8
Y1 - 2005/7/8
N2 - Non-small cell lung cancer frequently shows loss of heterozygosity of the chromosome 3p21.3 region and several genes such as RASSF1A, BLU, and SEMA3B have been identified as candidate tumor suppressor genes at this region since their downregulation and hypermethylation at their promoter regions were frequently detected in lung cancer. To determine whether these three genes are simultaneously inactivated during lung cancer development, we studied 138 primary non-small cell lung cancers for the promoter methylation status of these genes and allelic loss of the chromosome 3p21.3 region. We found promoter hypermethylation at 32% in RASSF1A, 30% in BLU, and 47% in SEMA3B. Allelic loss of 3p21.3 was detected in 54 (58%) of 93 informative tumors. Despite the weak association of methylation status among these three genes, there was no correlation between the methylation status of each gene and loss of heterozygosity. We also studied possible genes downstream of RASSF1A in 16 primary non-small cell lung cancers and found that the expressions of SM22 and SPARC were significantly downregulated in RASSF1A-hypermethylated tumors. Our results showed that, while candidate tumor suppressor genes at this locus can be simultaneously inactivated by epigenetic alterations, loss of heterozygosity without any hypermethylation of the three genes can also occur in some cases, suggesting that just one allelic loss might also be sufficient for the inactivation of any of these genes for lung cancer development.
AB - Non-small cell lung cancer frequently shows loss of heterozygosity of the chromosome 3p21.3 region and several genes such as RASSF1A, BLU, and SEMA3B have been identified as candidate tumor suppressor genes at this region since their downregulation and hypermethylation at their promoter regions were frequently detected in lung cancer. To determine whether these three genes are simultaneously inactivated during lung cancer development, we studied 138 primary non-small cell lung cancers for the promoter methylation status of these genes and allelic loss of the chromosome 3p21.3 region. We found promoter hypermethylation at 32% in RASSF1A, 30% in BLU, and 47% in SEMA3B. Allelic loss of 3p21.3 was detected in 54 (58%) of 93 informative tumors. Despite the weak association of methylation status among these three genes, there was no correlation between the methylation status of each gene and loss of heterozygosity. We also studied possible genes downstream of RASSF1A in 16 primary non-small cell lung cancers and found that the expressions of SM22 and SPARC were significantly downregulated in RASSF1A-hypermethylated tumors. Our results showed that, while candidate tumor suppressor genes at this locus can be simultaneously inactivated by epigenetic alterations, loss of heterozygosity without any hypermethylation of the three genes can also occur in some cases, suggesting that just one allelic loss might also be sufficient for the inactivation of any of these genes for lung cancer development.
UR - http://www.scopus.com/inward/record.url?scp=21144446552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21144446552&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2004.10.041
DO - 10.1016/j.canlet.2004.10.041
M3 - Article
C2 - 15922865
AN - SCOPUS:21144446552
SN - 0304-3835
VL - 225
SP - 131
EP - 139
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -