Lung cancer is the leading cause of cancer deaths among women and men in Taiwan.? However, the molecular mechanisms involved in lung tumorigenesis in Taiwan remain poorly defined.? Therefore, my laboratory investigates the etiological association of alterations in several tumor suppressor genes, oncogenes, and DNA repair genes with lung tumorigenesis in Taiwan.? These genes are p53 tumor suppressor gene, RB tumor suppressor gene, p16 tumor suppressor gene, K-ras oncogene, cyclin-dependent kinase genes, cyclin genes, as well as ERCC1~6, hMSH2, hMSH3, hMLH1, hPMS1, and hPMS2 repair genes.? The alteration analyses include the following aspects: gene mutation and polymorphism, gene loss, hypermethylation of promoter, mRNA alteration, and altered protein expression.? More recently, my laboratory has continued to do research on cancer genomics such as (1) genome-wide search of loss of heterozygosity (LOH) of microdissected primary lung tumors, (2) comparison of mRNA expression profiles between chemo-resistant and -sensitive lung cancer patients, and (3) genome-scanning approaches of DNA methylation profiles for identification of new genes critical to lung tumorigenesis.? In addition, we are developing more potential anti-cancer drugs such as indole derivatives, podophyllotoxin derivatives, DNA methyltransferase inhibitors, and histone deacetylase inhibitors using the cell and animal model.? We hope that the results of our molecular research can provide evidences of the etiological association of genetic alterations with lung tumorigenesis in Taiwan?? In addition, we hope that the results of our study will benefit the people suffered lung cancer and their affected families.

  H.-S. Hsu , Y.-C. Wang, R.-C. Tseng, J.-W. Chang, J.-T. Chen, C.-M. Shih , C.-Y. Chen, and Yi-Ching Wang * . 2004 . 5' CpG hypermethylation is responsible for p14 arf inactivation and inversely correlates with p 53 overexpression in resected non-small cell lung cancer . Clin. Cancer Res. , 10:4734-4741. (SCI 6.177)

C. Tzao, H.-Y. Tsai, J.-T. Cheng, C.-M. Shih, C.-Y. Chen, and Yi-Ching Wang * . 2004 . 5'CpG island hypermethylation and aberrant transcript splicing both contribute to the inactivation of the FHIT gene in resected non-small cell lung cancer. Eur. J. Cancer 40:2175-2183. (SCI4.167)

M.-N. Lee, R.-C. Tseng, H.-S. Hsu, J. Y. Chen, W. L. Ho, C. Tzao, Yi-Ching Wang. 2007. Epigenetic inactivation of the chromosomal stability control genes, BRCA1, BRCA2, and XRCC5 in non-small cell lung cancer. Clin. Cancer Res., 13:832-838 (SCI 6.177)

1st International Cancer Symposium (2007/11/16 ~ 2007/11/17, »OÆW)
Speech: Epigenomic alteration and its clinical implications in lung cancer.

1st Czech-Taiwan Workshop (2007/10/1 ~2007/10/2, »OÆW)
Speech: Global DNA methylation analysis in cancer: application on tumor-related gene identification and DNA methyltransferase deregulation analysis.

12th World Conference on Lung Cancer (2007/9/1 ~ 2007/9/5, ­ºº¸/Áú°ê)
Speech: GGenomic and epigenomic instabilities in lung cancer: molecular mechanism and clinical implications.

International Symposium on Biomarker Discovery in Human Cancers (2007/5/7, »OÆW)
Speech: Multiple genetic and epigenetic biomarkers in cytologically negative sputum and plasma for lung cancer detection and a nested case-control study for risk assessment.

Asia-Pacific Congress on Lung Cancer¡¨ (12/3~12/4/2006, »OÆW)
Speech: Genome-wide chromosomal deletion and promoter hypermethylation and their clinical implications in lung cancer.

America Association for Cancer Research (AACR) s pecial c onference in c ancer r esearch ¡X Chromatin, c hromosomes and c ancer e pigenetics. (2004/11/10 ~ 2004/11/14 ¬ü°ê )
Speech: Overexpression of DNA methyltransferase genes in lung cancer and their association with 5' CpG hypermethylation, p53 mutation, and clinical implications.

  21st International Academy of Tumor Marker Oncology Conference. (2004/8/21 ~ 2004/8/25 ¦è¦w / ¤¤°ê )
Speech: Wild-type p53 overexpression and its correlation with MDM2 and p14ARF alterations: an alternative pathway to non-small cell lung cancer .

Special S eminar at Department of Human Genetics, Ohio State University (2004/10/8 ¬ü°ê )
Speech: Inactivation of hMLH1 and hMSH2 by promoter methylation in primary non-small cell lung tumors and matched sputum samples.

Keystone Symposium on ¡§Epigenetics in Development and Disease¡¨ (2002/2/21 ~ 2002/2/26 ¬ü°ê )
Speech: Inactivation of h mlh 1 by genetic and epigenetic alterations, a novel mechanism causing non-small cell lung cancer.

Genetic/Epigenetic Alterations and candidate tumor suppressor gene identification in lung adenocarcinoma: analyses of allelic deletion, promoter hypermethylation, and chromatin alteration¡@(DOH94-TD-G-111-014)

The alteration of Wnt/£]-catenin pathway and its use as a therapeutic target for lung cancer
(NSC95-2320-B-006-087-MY3)

Cellular mechanism and animal study of novel modulable dendritic hybrids compounds on anti-cancer target molecular/pathway¡@(NSC95-2627-M-003-002-)

CpG island methylation alterations in relation to over activation of DNA methyltransferases: Mechanistic and clinical correlations and DNMT inhibitor studies