对两种最致命癌症基因组的探秘

据9月4日的《科学》杂志报道说，有2 项新的研究对助长正常细胞转变为2 种最致命癌症的基因组的变异进行了描述：它们是多形性胶质母细胞瘤（这是最常见类型的脑癌）和胰腺癌。尽管对每种癌症类型的特异性基因组变异每个肿瘤都有所不同，但这2 项研究披露了一个核心组的细胞信号通路和调节过程出现了偏差，从而导致了疾病的发生。在第一项研究中，D. Williams Parsons 及其同僚对来自22 个人类胶质母细胞瘤样本的2 万多个编码蛋白质的基因序列进行了分析，以期发现可能的变异。另外，他们还观察那些有着肿瘤特异性变化的基因表达谱以及被拷贝基因的数量。他们发现了多种的影响基因的变异，而这些变异从前并没有与这些肿瘤挂上钩。有一种叫做IDH1 的基因容易在所谓的“继发性胶质母细胞瘤”中发生变异，这种继发性胶质母细胞瘤起源于低度恶性的肿瘤，同时也出现于较年轻的病人中。在这一小型的研究中，病人的肿瘤如果有IDH1 变异的话会有较长的生存时间，这表明IDH1 基因是一种可用于筛选和治疗的有用的临床标记，尽管这些结果还需要在一个更大的实验分析中得到证实。在第２项研究中，同一批的科学家对胰腺癌的基因组成进行了调查。胰腺癌是一种常常在发现的时候已经处于晚期的癌症，而且对这种癌症的治疗方法十分匮乏。Sian Jones 及其同僚对24 例人类胰腺肿瘤的样本应用了相同的基因组策略，他们报道说，有一核心组的12 种细胞信号通路或调节过程在70-100%的这些肿瘤中都逐一出现了基因变异，表明这些通路的中断是胰腺肿瘤发展的重大特征的形成原因。文章的作者得出结论：“治疗研发的最大希望可能是发现以变异通路和过程的生理效应作为标靶的药物，而不是针对它们的个别基因组分的药物。”

ARTICLE #20: "An Integrated Genomic Analysis of Glioblastoma Multiforme," by D.W. Parsons; S. Jones; X. Zhang; J.C-H. Li; R.J. Leary; P. Angenendt; L.A. Diaz, Jr.; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at Ludwig Center for Cancer Genetics and Therapeutics in Baltimore, MD; D.W. Parsons; S. Jones; X. Zhang; J.C-H. Li; R.J. Leary; P. Angenendt; L.A. Diaz, Jr.; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at Howard Hughes Medical Institute in Baltimore, MD; D.W. Parsons; S. Jones; X. Zhang; J.C-H. Li; R.J. Leary; P. Angenendt; L.A. Diaz, Jr.; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at Johns Hopkins Kimmel Cancer Center in Baltimore, MD; D.W. Parsons at Baylor College of Medicine in Houston, TX; P. Mankoo; H. Carter; I-M. Sui; G. Gallia; A. Olivi; G.J. Riggins; R. Karchin at Johns Hopkins Medical Institutions in Baltimore, MD; R. McLendon; B.A. Rasheed; S. Keir; H. Yan; D.D. Bigner at Pediatric Brain Tumor Foundation in Durham, NC; R. McLendon; B.A. Rasheed; S. Keir; H. Yan; D.D. Bigner at Preston Robert Tisch Brain Tumor Center at Duke University Medical Center in Durham, NC; T. Nikolskaya at Vavilov Institute for General Genetics in Moscow, Russia; Y. Nikolsky at GeneGo, Inc. in St. Joseph, MI; D.A. Busam; H. Tekleab; R.L. Strausberg at J. Craig Venter Institute in Rockville, MD; J. Hartigan; D.R. Smith at Agencourt Bioscience Corporation in Beverly, MA; S.K.N. Marie; S.M.O. Shinjo at University of São Paulo School of Medicine in São Paulo, Brazil.

ARTICLE #21: "Pathways Underlying Pancreatic Tumorigenesis," by S. Jones; X. Zhang; D.W. Parsons; J.C-H. Lin; R.J. Leary; P. Angenendt; J.R. Eshleman; S.E. Kern; R.H. Hruban; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at The Sol Goldman Pancreatic Cancer Research Center in Baltimore, MD; S. Jones; X. Zhang; D.W. Parsons; J.C-H. Lin; R.J. Leary; P. Angenendt; J.R. Eshleman; S.E. Kern; R.H. Hruban; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at Ludwig Center for Cancer Genetics and Therapeutics in Baltimore, MD; S. Jones; X. Zhang; D.W. Parsons; J.C-H. Lin; R.J. Leary; P. Angenendt; J.R. Eshleman; S.E. Kern; R.H. Hruban; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at Howard Hughes Medical Institute in Baltimore, MD; S. Jones; X. Zhang; D.W. Parsons; J.C-H. Lin; R.J. Leary; P. Angenendt; J.R. Eshleman; S.E. Kern; R.H. Hruban; N. Papadopoulos; G. Parmigiani; B. Vogelstein; V.E. Velculescu; K.W. Kinzler at Johns Hopkins Kimmel Cancer Center in Baltimore, MD; D.W. Parsons at Baylor College of Medicine in Houston, TX; P. Mankoo; H. Carter; H. Kamiyama; A. Jimeno; S-M. Hong; B. Fu; M-T. Lin; E.S. Calhoun; M. Kamiyama; K. Walter; M. Hildago; S.D. Leach; A.P. Klein; E.M. Jaffee; M. Goggins; A. Maitra; C. Iacobuzio-Donahue; J.R. Eshleman; S.E. Kern; R.H. Hruban; R. Karchin at Johns Hopkins Medical Institutions in Baltimore, MD; T. Nikolskaya at Vavilov Institute for General Genetics in Moscow, Russia; Y. Nikolsky at GeneGo, Inc. in St. Joseph, MI; J. Hartigan; D.R. Smith at Agencourt Bioscience Corporation in Beverly, MA.