Suppl. Table 2 Genetic alterations and expression...
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Suppl. Table 2 Genetic alterations and expression profile of the PI3K p110α and the tumor suppressors PTEN, TP53, and RB in 3 SCLC cell lines PIK3CA PTEN TP53 RB activating mutation (1) wt (geno-/phenotype) (1) inactivating mutation: glu->stop (2) inactivating genetic alterations (3) (4) (5) H69 gene copy number 3.69 (6) phenotype: reduced TP53 protein expression (7) phenotype: reduced RB protein expression (8) phenotype: over-expressed protein (9) genotype wt (6) point mutation causing in disrupted splice site in TP53 (10) RB1 C706F mutation (10) H209 gene copy number 1.49 (6) phenotype: abberant RB protein expression (3, 11) phenotype wt (compared to normal pneumocytes) (9) phenotype wt (compared to normal pneumocytes) (9) WT (6) inactivating mutation: arg->gly (12) H510 gene copy number 3.17 (6) phenotype: absent RB protein (13) (11) phenotype wt (compared to normal pneumocytes) (9) phenotype wt (compared to normal pneumocytes) (9) References 1. Shibata, T., Kokubu, A., Tsuta, K., and Hirohashi, S. Oncogenic mutation of PIK3CA in small cell lung carcinoma: a potential therapeutic target pathway for chemotherapy-resistant lung cancer. Cancer Lett, 283: 203-211, 2009. 2. Hensel, C. H., Xiang, R. H., Sakaguchi, A. Y., and Naylor, S. L. Use of the single strand conformation polymorphism technique and PCR to detect p53 gene mutations in small cell lung cancer. Oncogene, 6: 1067-1071, 1991. 3. Hensel, C. H., Hsieh, C. L., Gazdar, A. F., Johnson, B. E., Sakaguchi, A. Y., Naylor, S. L., Lee, W. H., and Lee, E. Y. Altered structure and expression of the human retinoblastoma susceptibility gene in small cell lung cancer. Cancer Res, 50: 3067-3072, 1990. 4. Harbour, J. W., Lai, S. L., Whang-Peng, J., Gazdar, A. F., Minna, J. D., and Kaye, F. J. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science, 241: 353-357, 1988.
Transcript of Suppl. Table 2 Genetic alterations and expression...
Suppl. Table 2 Genetic alterations and expression profile of the PI3K p110α and the tumor suppressors PTEN, TP53, and RB in 3 SCLC cell lines
PIK3CA PTEN TP53 RB
activating mutation (1) wt (geno-/phenotype) (1) inactivating mutation: glu->stop (2) inactivating genetic alterations (3) (4) (5)
H69 gene copy number 3.69 (6) phenotype: reduced TP53 protein expression (7) phenotype: reduced RB protein expression (8)
phenotype: over-expressed protein (9)
genotype wt (6) point mutation causing in disrupted splice site in TP53 (10) RB1 C706F mutation (10)
H209 gene copy number 1.49 (6) phenotype: abberant RB protein expression (3, 11)
phenotype wt (compared to normal pneumocytes) (9) phenotype wt (compared to normal pneumocytes) (9)
WT (6) inactivating mutation: arg->gly (12)
H510 gene copy number 3.17 (6) phenotype: absent RB protein (13) (11)
phenotype wt (compared to normal pneumocytes) (9) phenotype wt (compared to normal pneumocytes) (9)
References
1. Shibata, T., Kokubu, A., Tsuta, K., and Hirohashi, S. Oncogenic mutation of PIK3CA in small cell lung carcinoma: a potential therapeutic target pathway for chemotherapy-resistant lung cancer. Cancer Lett, 283: 203-211, 2009.
2. Hensel, C. H., Xiang, R. H., Sakaguchi, A. Y., and Naylor, S. L. Use of the single strand conformation polymorphism technique and PCR to detect p53 gene mutations in small cell lung cancer. Oncogene, 6: 1067-1071, 1991.
3. Hensel, C. H., Hsieh, C. L., Gazdar, A. F., Johnson, B. E., Sakaguchi, A. Y., Naylor, S. L., Lee, W. H., and Lee, E. Y. Altered structure and expression of the human retinoblastoma susceptibility gene in small cell lung cancer. Cancer Res, 50: 3067-3072, 1990.
4. Harbour, J. W., Lai, S. L., Whang-Peng, J., Gazdar, A. F., Minna, J. D., and Kaye, F. J. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science, 241: 353-357, 1988.
5. Yokota, J., Akiyama, T., Fung, Y. K., Benedict, W. F., Namba, Y., Hanaoka, M., Wada, M., Terasaki, T., Shimosato, Y., Sugimura, T., and et al. Altered expression of the retinoblastoma (RB) gene in small-cell carcinoma of the lung. Oncogene, 3: 471-475, 1988.
6. Yamamoto, H., Shigematsu, H., Nomura, M., Lockwood, W. W., Sato, M., Okumura, N., Soh, J., Suzuki, M., Wistuba, II, Fong, K. M., Lee, H., Toyooka, S., Date, H., Lam, W. L., Minna, J. D., and Gazdar, A. F. PIK3CA mutations and copy number gains in human lung cancers. Cancer Res, 68: 6913-6921, 2008.
7. Han, J. Y., Chung, Y. J., Park, S. W., Kim, J. S., Rhyu, M. G., Kim, H. K., and Lee, K. S. The relationship between cisplatin-induced apoptosis and p53, bcl-2 and bax expression in human lung cancer cells. Korean J Intern Med, 14: 42-52, 1999.
8. Rygaard, K., Sorenson, G. D., Pettengill, O. S., Cate, C. C., and Spang-Thomsen, M. Abnormalities in structure and expression of the retinoblastoma gene in small cell lung cancer cell lines and xenografts in nude mice. Cancer Res, 50: 5312-5317, 1990.
9. Arcaro, A., Khanzada, U. K., Vanhaesebroeck, B., Tetley, T. D., Waterfield, M. D., and Seckl, M. J. Two distinct phosphoinositide 3-kinases mediate polypeptide growth factor-stimulated PKB activation. EMBO J, 21: 5097-5108, 2002.
10. Pleasance, E. D., Stephens, P. J., O'Meara, S., McBride, D. J., Meynert, A., Jones, D., Lin, M. L., Beare, D., Lau, K. W., Greenman, C., Varela, I., Nik-Zainal, S., Davies, H. R., Ordonez, G. R., Mudie, L. J., Latimer, C., Edkins, S., Stebbings, L., Chen, L., Jia, M., Leroy, C., Marshall, J., Menzies, A., Butler, A., Teague, J. W., Mangion, J., Sun, Y. A., McLaughlin, S. F., Peckham, H. E., Tsung, E. F., Costa, G. L., Lee, C. C., Minna, J. D., Gazdar, A., Birney, E., Rhodes, M. D., McKernan, K. J., Stratton, M. R., Futreal, P. A., and Campbell, P. J. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature, 463: 184-190, 2010.
11. Modi, S., Kubo, A., Oie, H., Coxon, A. B., Rehmatulla, A., and Kaye, F. J. Protein expression of the RB-related gene family and SV40 large T antigen in mesothelioma and lung cancer. Oncogene, 19: 4632-4639, 2000.
12. D'Amico, D., Carbone, D., Mitsudomi, T., Nau, M., Fedorko, J., Russell, E., Johnson, B., Buchhagen, D., Bodner, S., Phelps, R., and et al. High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene, 7: 339-346, 1992.
13. Horowitz, J. M., Park, S. H., Bogenmann, E., Cheng, J. C., Yandell, D. W., Kaye, F. J., Minna, J. D., Dryja, T. P., and Weinberg, R. A. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. Proc Natl Acad Sci U S A, 87: 2775-2779, 1990.
