Inactivation of LLC1 Gene in Nonsmall Cell Lung Cancer

Overview

Journal Int J Cancer

Specialty Oncology

Date 2007 Feb 17

PMID 17304513

Citations 6

Authors

Kyeong-Man Hong

Sei-Hoon Yang

Sinchita Roy Chowdhuri

Audrey Player

Megan Hames

Junya Fukuoka

Daoud Meerzaman

Tatiana Dracheva

Zhifu Sun

Ping Yang

Jin Jen

Affiliations

Soon will be listed here.

Abstract

Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis.

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References

Wang T, Fan L, Watanabe Y, McNeill P, Fanger G, Persing D . L552S, an alternatively spliced isoform of XAGE-1, is over-expressed in lung adenocarcinoma. Oncogene. 2001; 20(53):7699-709. DOI: 10.1038/sj.onc.1204939. View

Beer D, Kardia S, Huang C, Giordano T, Levin A, Misek D . Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat Med. 2002; 8(8):816-24. DOI: 10.1038/nm733. View

Agathanggelou A, Dallol A, Zochbauer-Muller S, Morrissey C, Honorio S, Hesson L . Epigenetic inactivation of the candidate 3p21.3 suppressor gene BLU in human cancers. Oncogene. 2003; 22(10):1580-8. DOI: 10.1038/sj.onc.1206243. View

Holst C, Nuovo G, Esteller M, Chew K, Baylin S, Herman J . Methylation of p16(INK4a) promoters occurs in vivo in histologically normal human mammary epithelia. Cancer Res. 2003; 63(7):1596-601. View

Hodgson J, Chin K, Collins C, Gray J . Genome amplification of chromosome 20 in breast cancer. Breast Cancer Res Treat. 2003; 78(3):337-45. DOI: 10.1023/a:1023085825042. View

Player A, Gillespie J, Fujii T, Fukuoka J, Dracheva T, Meerzaman D . Identification of TDE2 gene and its expression in non-small cell lung cancer. Int J Cancer. 2003; 107(2):238-43. DOI: 10.1002/ijc.11391. View

Sasaki H, Moriyama S, Mizuno K, Yukiue H, Yano M, Fukai I . SAGE mRNA expression in advanced-stage lung cancers. Eur J Surg Oncol. 2003; 29(10):900-3. DOI: 10.1016/j.ejso.2003.06.001. View

Herman J, Baylin S . Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003; 349(21):2042-54. DOI: 10.1056/NEJMra023075. View

Koga T, Horio Y, Mitsudomi T, Takahashi T, Yatabe Y . Identification of MGB1 as a marker in the differential diagnosis of lung tumors in patients with a history of breast cancer by analysis of publicly available SAGE data. J Mol Diagn. 2004; 6(2):90-5. PMC: 1867472. DOI: 10.1016/S1525-1578(10)60495-3. View

10.

Fukuoka J, Fujii T, Shih J, Dracheva T, Meerzaman D, Player A . Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer. Clin Cancer Res. 2004; 10(13):4314-24. DOI: 10.1158/1078-0432.CCR-03-0489. View

11.

He P, Varticovski L, Bowman E, Fukuoka J, Welsh J, Miura K . Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Hum Pathol. 2004; 35(10):1196-209. DOI: 10.1016/j.humpath.2004.06.014. View

12.

Velculescu V, Zhang L, Vogelstein B, Kinzler K . Serial analysis of gene expression. Science. 1995; 270(5235):484-7. DOI: 10.1126/science.270.5235.484. View

13.

Merlo A, Herman J, Mao L, Lee D, Gabrielson E, Burger P . 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995; 1(7):686-92. DOI: 10.1038/nm0795-686. View

14.

Herman J, Graff J, Myohanen S, Nelkin B, Baylin S . Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A. 1996; 93(18):9821-6. PMC: 38513. DOI: 10.1073/pnas.93.18.9821. View

15.

Zhang L, Zhou W, Velculescu V, Kern S, Hruban R, Hamilton S . Gene expression profiles in normal and cancer cells. Science. 1997; 276(5316):1268-72. DOI: 10.1126/science.276.5316.1268. View

16.

Hibi K, Liu Q, Beaudry G, Madden S, Westra W, Wehage S . Serial analysis of gene expression in non-small cell lung cancer. Cancer Res. 1998; 58(24):5690-4. View

17.

Hibi K, Westra W, Borges M, Goodman S, Sidransky D, Jen J . PGP9.5 as a candidate tumor marker for non-small-cell lung cancer. Am J Pathol. 1999; 155(3):711-5. PMC: 1866887. DOI: 10.1016/S0002-9440(10)65169-3. View

18.

Dammann R, Schagdarsurengin U, Seidel C, Strunnikova M, Rastetter M, Baier K . The tumor suppressor RASSF1A in human carcinogenesis: an update. Histol Histopathol. 2005; 20(2):645-63. DOI: 10.14670/HH-20.645. View

19.

Hong K, Yang S, Guo M, Herman J, Jen J . Semiautomatic detection of DNA methylation at CpG islands. Biotechniques. 2005; 38(3):354, 356, 358. DOI: 10.2144/05383BM02. View

20.

Yang S, Mechanic L, Yang P, Landi M, Bowman E, Wampfler J . Mutations in the tyrosine kinase domain of the epidermal growth factor receptor in non-small cell lung cancer. Clin Cancer Res. 2005; 11(6):2106-10. DOI: 10.1158/1078-0432.CCR-04-1853. View