Tuberc Respir Dis.  2012 Sep;73(3):137-142. 10.4046/trd.2012.73.3.137.

Year-in-Review of Lung Cancer

• Son JW

• KMID: 1842908
• DOI: http://doi.org/10.4046/trd.2012.73.3.137

Abstract

In the last several years, we have made slow but steady progress in understanding molecular biology of lung cancer. This review is focused on advances in understanding the biology of lung cancer that have led to proof of concept studies on new therapeutic approaches. The three selected topics include genetics, epigenetics and non-coding RNA. This new information represents progress in the integration of molecular mechanisms that to identify more effective ways to target lung cancer.

Keyword

Lung Neoplasms; Molecular Biology; Genetics; Epigenomics; RNA, Untranslated

MeSH Terms

Biology
Epigenomics
Lung
Lung Neoplasms
Molecular Biology
RNA, Untranslated
RNA, Untranslated

Figure

• 

  Figure 1 Gene expression via genetic, epigenetic and posttranscriptional modification is a key regulatory process in the cell.

• 

  Figure 2 Enzymatic conversion of cytosine to 5-hydroxymethylcytosine. DNA methyltransferases (DNMTs) convert cytosine to 5-methylcytosine. 5-hydroxymethylcytosine be converted to 5-hydroxymethylcytosine in an enzymatic process involving members of the ten-eleven translocation (TET) protein family. 5-hydroxymethylcytosine could be converted to cytosine through a passive demethylation or an active demethylation pathway.

• 

  Figure 3 Schematic diagram of the four archetypes of longer ncRNAs (lncRNA) mechanism. Signaling: LncRNA expression can be stimulated in response to certain stimuli, such as cellular stress and temperature. Decoys: Specific lncRNAs are transcribed and then bind to and titrate away protein factors. Guides: LncRNAs can be molecular guides by localizing particular ribonucleoprotein complexes to specific chromatin targets. Scaffolds: LncRNAs can bring together multiple proteins to form ribonucleoprotein complexes. Adopted from Wang and Chang19. Mol Cell 2011;43:904-14.

• 

  Figure 4 MicroRNAs (miRNAs) as new characters in the plot between epigenetics and lung cancer.

Reference

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010. 60:277–300.

2. Spiro SG, Silvestri GA. One hundred years of lung cancer. Am J Respir Crit Care Med. 2005. 172:523–529.

3. Kulesza P, Ramchandran K, Patel JD. Emerging concepts in the pathology and molecular biology of advanced non-small cell lung cancer. Am J Clin Pathol. 2011. 136:228–238.

4. Govindan R. Summary of presentation from the targeted therapy in lung cancer meeting. J Thorac Oncol. 2011. 6:11 Suppl 4. S1757.

5. Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010. 11:685–696.

6. Lipson D, Capelletti M, Yelensky R, Otto G, Parker A, Jarosz M, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med. 2012. 18:382–384.

7. Ju YS, Lee WC, Shin JY, Lee S, Bleazard T, Won JK, et al. A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res. 2012. 22:436–445.

8. Jung Y, Kim P, Jung Y, Keum J, Kim SN, Choi YS, et al. Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing. Genes Chromosomes Cancer. 2012. 51:590–597.

9. Togashi Y, Soda M, Sakata S, Sugawara E, Hatano S, Asaka R, et al. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One. 2012. 7:e31323.

10. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002. 3:415–428.

11. Son JW, Kim YJ, Cho HM, Lee SY, Lee SM, Kang JK, et al. Promoter hypermethylation of the CFTR gene and clinical/pathological features associated with non-small cell lung cancer. Respirology. 2011. 16:1203–1209.

12. Gery S, Komatsu N, Kawamata N, Miller CW, Desmond J, Virk RK, et al. Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer. Clin Cancer Res. 2007. 13:1399–1404.

13. Hamilton JP. Epigenetics: principles and practice. Dig Dis. 2011. 29:130–135.

14. Williams K, Christensen J, Helin K. DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep. 2012. 13:28–35.

15. Jin SG, Jiang Y, Qiu R, Rauch TA, Wang Y, Schackert G, et al. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations. Cancer Res. 2011. 71:7360–7365.

16. Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, et al. Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. Cancer Sci. 2012. 103:670–676.

17. Eddy SR. Non-coding RNA genes and the modern RNA world. Nat Rev Genet. 2001. 2:919–929.

18. ENCODE Project Consortium. Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007. 447:799–816.

19. Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011. 43:904–914.

20. Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011. 10:38.

21. Schmidt LH, Spieker T, Koschmieder S, Schäffers S, Humberg J, Jungen D, et al. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol. 2011. 6:1984–1992.

22. Sato F, Tsuchiya S, Meltzer SJ, Shimizu K. MicroRNAs and epigenetics. FEBS J. 2011. 278:1598–1609.

23. Watanabe K, Emoto N, Hamano E, Sunohara M, Kawakami M, Kage H, et al. Genome structure-based screening identified epigenetically silenced microRNA associated with invasiveness in non-small-cell lung cancer. Int J Cancer. 2012. 130:2580–2590.

24. Incoronato M, Urso L, Portela A, Laukkanen MO, Soini Y, Quintavalle C, et al. Epigenetic regulation of miR-212 expression in lung cancer. PLoS One. 2011. 6:e27722.

25. Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Setién F, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 2007. 67:1424–1429.

26. Zhang JG, Guo JF, Liu DL, Liu Q, Wang JJ. MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2. J Thorac Oncol. 2011. 6:671–678.

27. Jeon HS, Lee SY, Lee EJ, Yun SC, Cha EJ, Choi E, et al. Combining microRNA-449a/b with a HDAC inhibitor has a synergistic effect on growth arrest in lung cancer. Lung Cancer. 2012. 76:171–176.

28. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007. 104:15805–15810.