Modeling genomic diversity and tumor dependency in malignant melanoma

被引:230
|
作者
Lin, William M. [1 ,2 ,5 ]
Baker, Alissa C. [1 ,2 ]
Beroukhim, Rameen [1 ,2 ,5 ]
Winckler, Wendy [1 ,2 ,5 ]
Feng, Whei [1 ,2 ,5 ]
Marmion, Jennifer M. [7 ]
Laine, Elisabeth [8 ]
Greulich, Heidi [1 ,2 ,5 ]
Tseng, Hsiuyi [1 ,2 ]
Gates, Casey [5 ]
Hodi, F. Stephen [2 ]
Dranoff, Glenn [2 ]
Sellers, William R. [2 ,6 ]
Thomas, Roman K. [9 ,10 ,11 ,12 ]
Meyerson, Matthew [1 ,2 ,4 ,5 ]
Golub, Todd R. [1 ,3 ,5 ]
Dummer, Reinhard
Herlyn, Meenhard [7 ]
Getz, Gad [1 ,5 ]
Garraway, Levi A. [1 ,2 ,5 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[5] MIT & Harvard, Broad Inst, Cambridge, MA 02139 USA
[6] Novartis Inst Biomed Res, Cambridge, MA 02139 USA
[7] Wistar Inst Anat & Biol, Div Canc Biol, Philadelphia, PA 19104 USA
[8] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland
[9] Max Planck Soc, Klaus Joachim Zulch Labs, Max Planck Inst Neurol Res, Cologne, Germany
[10] Univ Cologne, Fac Med, Cologne, Germany
[11] Univ Cologne, Ctr Integrated Oncol, Cologne, Germany
[12] Univ Cologne, Dept Internal Med 1, Cologne, Germany
基金
英国惠康基金;
关键词
D O I
10.1158/0008-5472.CAN-07-2615
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors.
引用
收藏
页码:664 / 673
页数:10
相关论文
共 50 条
  • [1] From genomic diversity to tumor dependency in human cancer
    Garraway, Levi
    MOLECULAR CANCER THERAPEUTICS, 2007, 6 (12) : 3634S - 3634S
  • [2] Deciphering the genomic heterogeneity and evolution in malignant melanoma by genomic profiling of clonal tumor populations
    Lorber, Thomas
    Dietsche, Tanja
    Perrina, Valeria
    Barret, Michael
    Glatz, Kathrin
    Ruiz, Christian
    Bubendorf, Lukas
    CANCER RESEARCH, 2014, 74 (19)
  • [3] Genomic comparison of malignant melanoma and atypical Spitz tumor in the pediatric population
    Church, Alanna J.
    Moustafa, Danna
    Pinches, Robert Seth
    Hawryluk, Elena B.
    Schmidt, Birgitta A. R.
    PEDIATRIC DERMATOLOGY, 2022, 39 (03) : 409 - 419
  • [4] Genomic Landscape of Malignant Peripheral Nerve Sheath Tumor-Like Melanoma
    Muniz, Thiago P.
    Sorotsky, Hadas
    Kanjanapan, Yada
    Rose, April A. N.
    Araujo, Daniel, V
    Fortuna, Alexander
    Ghazarian, Danny
    Kamil, Zaid Saeed
    Pugh, Trevor
    Mah, Michelle
    Thiagarajah, Madhuran
    Torti, Dax
    Spreafico, Anna
    Hogg, David
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2021, 141 (10) : 2470 - 2479
  • [5] Comparative genomic hybridization in malignant melanoma
    Fischer, J
    Schanz, S
    Ulmer, A
    Yildiz, M
    Fierlbeck, G
    Klein, CA
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 125 (03) : A27 - A27
  • [6] Genomic stability in malignant melanoma of Xiphophorus
    Zunker, K
    Epplen, JT
    Schartl, M
    MELANOMA RESEARCH, 2006, 16 (02) : 105 - 113
  • [7] Genomic landscape of malignant peripheral nerve sheath tumor (MPNST)-like melanoma.
    Muniz, Thiago Pimentel
    Sorotsky, Hadas
    Kanjanapan, Yada
    Rose, April A. N.
    Araujo, Daniel Vilarim
    Fortuna, Alexander
    Ghazarian, Danny K.
    Kamil, Zaid Saeed
    Pugh, Trevor John
    Mah, Michelle
    Thiagarajah, Madhuran
    Spreafico, Anna
    Hogg, David
    JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (15)
  • [8] TUMOR ANTIGENS IN MALIGNANT MELANOMA
    NATHANSO.L
    SCHWARTZ, RS
    ANNALS OF INTERNAL MEDICINE, 1971, 74 (05) : 837 - +
  • [9] HISTOLOGIC DIVERSITY OF MALIGNANT-MELANOMA
    LISTROM, MB
    FOUCAR, CE
    AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 1990, 94 (06) : 803 - 804
  • [10] Malignant melanoma: genetics and therapeutics in the genomic era
    Chin, Lynda
    Garraway, Levi A.
    Fisher, David E.
    GENES & DEVELOPMENT, 2006, 20 (16) : 2149 - 2182