DF/HCC Program Affiliation

Lymphoma and Myeloma
Lung Cancer
Cancer Genetics

Research Abstract

The Meyerson laboratory studies human lung tumors by genetic, genomic, and functional approaches. We are engaged in a systematic effort to identify gene alterations that cause lung cancer. As part of these efforts, we are sequencing protein kinase in lung cancer and other human cancers, in a large-scale effort in collaboration with the Sellers laboratory and the Broad Institute. Our first result was the identification of BRAF mutations in lung adenocarcinoma (Naoki et al., 2002). More recently, we have discovered common EGFR mutations in lung adenocarcinoma and showed that these mutations are closely correlated with clinical response to the EGFR kinase inhibitor, gefitinib (Paez et al. , 2004). As a complement, we are applying single nucleotide polymorphism (SNP) arrays to identify loss-of-heterozygosity (Lindblad-Toh et al., 2000) and copy number alterations (Zhao et al., 2004) in lung cancer. To search for tumor viruses, we have developed and are applying a new approach to pathogen discovery, computational subtraction (Weber et al., 2002; Xu et al., 2003). Finally, we are continuing our efforts to develop a rational classification system for lung carcinoma based on gene expression analysis (Bhattacharjee et al., 2001).

Our functional studies are concentrated on known tumor suppressor genes and on the oncogenes and tumor suppressor genes identified in our genomic screens. In particular, we have been engaged in biochemical analyses to determine the function of the multiple endocrine neoplasia type 1 (MEN-1) gene and its protein product, menin. We have identified a histone methyltransferase complex associated with menin and have shown that this complex is bound to target gene loci, Hoxc6 and Hoxc8 (Hughes et al., 2004). We are now extending our biochemical studies on menin, EGFR, and other proteins.

Publications

• Yuza Y, Glatt KA, Jiang J, Greulich H, Minami Y, Woo MS, Shimamura T, Shapiro G, Lee JC, Ji H, Feng W, Chen TH, Yanagisawa H, Wong KK, Meyerson M.Allele-Dependent Variation in the Relative Cellular Potency of Distinct EGFR Inhibitors.Cancer Biol Ther 2007
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• George RE, Attiyeh EF, Li S, Moreau LA, Neuberg D, Li C, Fox EA, Meyerson M, Diller L, Fortina P, Look AT, Maris JM.Genome-Wide Analysis of Neuroblastomas using High-Density Single Nucleotide Polymorphism Arrays.PLoS ONE 2007;2:e255.
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• Thomas RK, Nickerson E, Simons JF, Janne PA, Tengs T, Yuza Y, Garraway LA, LaFramboise T, Lee JC, Shah K, O'Neill K, Sasaki H, Lindeman N, Wong KK, Borras AM, Gutmann EJ, Dragnev KH, DeBiasi R, Chen TH, Glatt KA, Greulich H, Desany B, Lubeski CK, Brockman
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• Greulich H, Chen TH, Feng W, Jänne PA, Alvarez JV, Zappaterra M, Bulmer SE, Frank DA, Hahn WC, Sellers WR, Meyerson M.Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants.PLoS Med 2005 Oct 4;2(11):e313.
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• Zhao X, Weir BA, LaFramboise T, Lin M, Beroukhim R, Garraway L, Beheshti J, Lee JC, Naoki K, Richards WG, Sugarbaker D, Chen F, Rubin MA, Jänne PA, Girard L, Minna J, Christiani D, Li C, Sellers WR, Meyerson M.Homozygous deletions and chromosome amplifica
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• Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M.EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Ther
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• Hughes CM, Rozenblatt-Rosen O, Milne TA, Copeland TD, Levine SS, Lee JC, Hayes DN, Shanmugam KS, Bhattacharjee A, Biondi CA, Kay GF, Hayward NK, Hess JL, Meyerson M.Menin associates with a trithorax family histone methyltransferase complex and with the ho
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• Weber G, Shendure J, Tanenbaum DM, Church GM, Meyerson M.Identification of foreign gene sequences by transcript filtering against the human genome.Nat Genet 2002 Feb;30(2):141-2.
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