DF/HCC Program Affiliation

Member, Lymphoma and Myeloma Program
Member, Cancer Genetics Program
Member, Lung Cancer Program

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

• Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R, Lin WM, Province MA, Kraja A, Johnson LA, Shah K, Sato M, Thomas RK, Barletta JA, Borecki IB, Broderick S, Chang AC, Chiang DY, Chirieac LR, Cho J, Fujii Y, Gazdar AF, Giordano T, Greulich H, Hanna M. Characterizing the cancer genome in lung adenocarcinoma. Nature 2007 Dec 6; 450(7171):893-8
  PMID: 17982442
• Meyerson M. Cancer: broken genes in solid tumours. Nature 2007 Aug 2; 448(7153):545-6
  PMID: 17671492
• 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 May 13; 6(5)
  PMID: 17495523
• 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
  PMID: 17327916
• Thomas RK, Nickerson E, Simons JF, Jänne 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. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nat Med 2006 Jul; 12(7):852-855
  PMID: 16799556
• 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
  PMID: 16187797
• 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 amplifications in human lung carcinomas revealed by single nucleotide polymorphism array analysis. Cancer Res 2005 Jul 1; 65(13):5561-70
  PMID: 15994928
• 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 Therapy. Science 2004 Apr 29;
  PMID: 15118125
• 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 hoxc8 locus. Mol Cell 2004 Feb 27; 13(4):587-97
  PMID: 14992727
• 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
  PMID: 11788827