Abstract
Lung cancer is a devastating illness, and very few of the advances in chemotherapeutics have enhanced survival over the past decade. In order to make an impact on this disease, we must understand the molecular abnormalities to target better therapeutics. In this chapter, we will describe the better understanding at the molecular level that has been gained for lung cancer and its prognosis. Over the last decade, advances in molecular biology have provided important information about potentially significant determinants of prognosis in lung cancer (1,2). These molecular biomarkers are typically expressed in neoplastic lung tissue. Molecular abnormalities include chromosomal aberrations, telomerase expression, expression of oncogenes, and loss of tumor suppressor genes. Based on the understanding of the abnormalities at the cellular and molecular levels, newer therapies can be pursued.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Salgia, R. and Skarin, A. T. (1998) Molecular abnormalities in lung cancer. J. Clin. Oncol. 16, 1207ā1217.
Mountain, C. F. (1995) New prognostic factors in lung cancer. Biologic prophets of cancer cell aggression. Chest 108, 246ā254.
Devereux, T. R., Taylor, J. A., and Barrett, J. C. (1996) Molecular mechanisms of lung cancer. Interaction of environmental and genetic factors. Giles F. Filley Lecture. Chest 109, 14Sā19S.
Hibi, K., Takahashi, T., Yamakawa, K., Ueda, R., Sekido, Y., Ariyoshi, Y., et al. (1992) Three distinct regions involved in 3p deletion in human lung cancer. Oncogene 7, 445ā449.
Otterson, G., Lin, A., and Kay, F. (1992) Genetic etiology of lung cancer. Oncology (Huntingt). 6, 97ā104, 107; discussion 108, 111ā112.
Sozzi, G., Veronese, M. L., Negrini, M., Baffa, R., Cotticelli, M. G., Inoue, H., et al. (1996) The FHIT gene 3p14.2 is abnormal in lung cancer. Cell 85, 17ā26.
Ohata, H., Emi, M., Fujiwara, Y., Higashino, K., Nakagawa, K., Futagami, R., et al. (1993) Deletion mapping of the short arm of chromosome 8 in non-small cell lung carcinoma. Genes Chromosomes Cancer 7, 85ā88.
Merlo, A., Gabrielson, E., Askin, F., and Sidransky, D. (1994) Frequent loss of chromosome 9 in human primary non-small cell lung cancer. Cancer Res. 54, 640ā642.
Shapiro, G. I. and Rollins, B. J. (1996) p16INK4A as a human tumor suppressor. Biochim. Biophys. Acta. 1242, 165ā169.
Fong, K. M., Zimmerman, P. V., and Smith, P. J. (1995) Lung pathology: the molecular genetics of non-small cell lung cancer. Pathology 27, 295ā301.
Meyerson, M. (2000) Role of telomerase in normal and cancer cells. J. Clin. Oncol. 18, 2626ā2634.
Carbone, D. P. (1997) The biology of lung cancer. Semin. Oncol. 24, 388ā401.
Hiyama, K., Ishioka, S., Shirotani, Y., Inai, K., Hiyama, E., Murakami, I., et al. (1995) Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb. Oncogene 10, 937ā944.
Yahata, N., Ohyashiki, K., Ohyashiki, J. H., Iwama, H., Hayashi, S., Ando, K., et al. (1998) Telomerase activity in lung cancer cells obtained from bronchial washings. J. Natl. Cancer Inst. 90, 684ā690.
Slebos, R. J., Kibbelaar, R. E., Dalesio, O., Kooistra, A., Stam, J., Meijer, C. J., et al. (1990) K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N. Engl. J. Med. 323, 561ā565.
Rosell, R., Li, S., Skacel, Z., Mate, J. L., Maestre, J., Canela, M., et al. (1993) Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients. Oncogene 8, 2407ā2412.
Mitsudomi, T., Steinberg, S. M., Oie, H. K., Mulshine, J. L., Phelps, R., Viallet, J., et al. (1991) ras gene mutations in non-small cell lung cancers are associated with shortened survival irrespective of treatment intent. Cancer Res. 51, 4999ā5002.
Graziano, S. L., Gamble, G. P., Newman, N. B., Abbott, L. Z., Rooney, M., Mookherjee, S., et al. (1999) Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer. J. Clin. Oncol. 17, 668ā675.
Greatens, T. M., Niehans, G. A., Rubins, J. B., Jessurun, J., Kratzke, R. A., Maddaus, M. A., and Niewoehner, D. E. (1998) Do molecular markers predict survival in non-small-cell lung cancer?. Am. J. Respir. Crit. Care Med. 157, 1093ā1097.
Paget, S. (1989) The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev. 8, 98ā101.
Prins, J., De Vries, E. G., and Mulder, N. H. (1993) The myc family of oncogenes and their presence and importance in small-cell lung carcinoma and other tumour types. Anticancer Res. 13, 1373ā1385.
Brennan, J., OāConnor, T., Makuch, R. W., Simmons, A. M., Russell, E., Linnoila, R. I., et al. (1991) myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens. Cancer Res. 51, 1708ā1712.
Noguchi, M., Hirohashi, S., Hara, F., Kojima, A., Shimosato, Y., Shinkai, T., and Tsuchiya, R. (1990) Heterogenous amplification of myc family oncogenes in small cell lung carcinoma. Cancer 66, 2053ā2058.
Funa, K., Steinholtz, L., Nou, E., and Bergh, J. (1987) Increased expression of N-myc in human small cell lung cancer biopsies predicts lack of response to chemotherapy and poor prognosis. Am. J. Clin. Pathol. 88, 216ā220.
Johnson, B. E., Ihde, D. C., Makuch, R. W., Gazdar, A. F., Carney, D. N., Oie, H., et al. (1987) myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J. Clin. Invest. 79, 1629ā1634.
Takahashi, T., Obata, Y., Sekido, Y., Hida, T., Ueda, R., Watanabe, H., et al. (1989) Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics. Cancer Res. 49, 2683ā2688.
Slebos, R. J., Evers, S. G., Wagenaar, S. S., and Rodenhuis, S. (1989) Cellular protoonocogenes are infrequently amplified in untreated non-small cell lung cancer. Br. J. Cancer 59, 76ā80.
Kawashima, K., Nomura, S., Hirai, H., Fukushi, S., Karube, T., Takeuchi, K., et al. (1992) Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung-cancer patients. Int. J. Cancer 50, 557ā561.
Kern, J. A., Schwartz, D. A., Nordberg, J. E., Weiner, D. B., Greene, M. I., Torney, L., and Robinson, R. A. (1990) p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res. 50, 5184ā5187.
Kern, J. A. and Filderman, A. E. (1993) Oncogenes and growth factors in human lung cancer. Clin. Chest Med. 14, 31ā41.
Pezzella, F., Turley, H., Kuzu, I., Tungekar, M. F., Dunnill, M. S., Pierce, C. B., et al. (1993) bcl-2 protein in non-small-cell lung carcinoma. N. Engl. J. Med. 329, 690ā694.
Uren, A. G. and Vaux, D. L. (1996) Molecular and clinical aspects of apoptosis. Pharmacol. Ther. 72, 37ā50.
Sidransky, D. and Hollstein, M. (1996) Clinical implications of the p53 gene. Annu. Rev. Med. 47, 285ā301.
Mitsudomi, T., Lam, S., Shirakusa, T., and Gazdar, A. F. (1993) Detection and sequencing of p53 gene mutations in bronchial biopsy samples in patients with lung cancer. Chest 104, 362ā365.
Lee, J. S., Yoon, A., Kalapurakal, S. K., Ro, J. Y., Lee, J. J., Tu, N., et al. (1995) Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor. J. Clin. Oncol. 13, 1893ā1903.
Yoshikawa, H., Nagashima, M., Khan, M. A., McMenamin, M. G., Hagiwara, K., and Harris, C. C. (1999) Mutational analysis of p73 and p53 in human cancer cell lines. Oncogene 18, 3415ā3421.
Osada, M., Ohba, M., Kawahara, C., Ishioka, C., Kanamaru, R., Katoh, I., et al. (1998) Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat. Med. 4, 839ā843.
Knudson, A. G., Jr. (1989) The ninth Gordon Hamilton-Fairley memorial lecture. Hereditary cancers: clues to mechanisms of carcinogenesis. Br. J. Cancer 59, 661ā666.
Yokota, J., Akiyama, T., Fung, Y. K., Benedict, W. F., Namba, Y., Hanaoka, M., et al. (1988) Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung. Oncogene 3, 471ā475.
Harbour, J. W., Lai, S. L., Whang-Peng, J., Gazdar, A. F., Minna, J. D., and Kaye, F. J. (1988) Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 241, 353ā357.
Shimizu, E., Coxon, A., Otterson, G. A., Steinberg, S. M., Kratzke, R. A., Kim, Y. W., et al. (1994) RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulmonary small cell carcinoma, and mesothelioma. Oncogene 9, 2441ā2448.
Xu, H. J., Hu, S. X., Cagle, P. T., Moore, G. E., and Benedict, W. F. (1991) Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas. Cancer Res. 51, 2735ā2739.
Kratzke, R. A., Greatens, T. M., Rubins, J. B., Maddaus, M. A., Niewoehner, D. E., Niehans, G. A., and Geradts, J. (1996) Rb and p16INK4A expression in resected non-small cell lung tumors. Cancer Res. 56, 3415ā3420.
Serrano, M., Hannon, G. J., and Beach, D. (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366, 704ā707.
Hannon, G. J. and Beach, D. (1994) p15INK4B is a potential effector of TGF-Ī²-induced cell cycle arrest. Nature 371, 257ā261.
Shapiro, G. I., Edwards, C. D., Kobzik, L., Godleski, J., Richards, W., Sugarbaker, D. J., and Rollins, B. J. (1995) Reciprocal Rb inactivation and p16INK4A expression in primary lung cancers and cell lines. Cancer Res. 55, 505ā509.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2003 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Kijima, T., Maulik, G., Salgia, R. (2003). Molecular Alterations in Lung Cancer. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicineā¢, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-324-0:29
Download citation
DOI: https://doi.org/10.1385/1-59259-324-0:29
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-0-89603-920-9
Online ISBN: 978-1-59259-324-8
eBook Packages: Springer Protocols