肿瘤基因组学(英语:oncogenomics)又称癌症基因组学(英语:cancer genomics)是基因组学中一门新兴的子学科,主要是通过高通量测序技术来将基因与癌症关联起来的学问。肿瘤是一种由 DNA 变异不断累积而导致细胞发生不受控激增并形成新生物的疾病。肿瘤基因组学的主要目标是通过鉴定新的原癌基因或者抑癌基因来为肿瘤诊断、肿瘤临床结果预测和肿瘤靶标治疗提供新的方法。肿瘤基因组学的应用导致了诸如伊马替尼、曲妥珠单抗和安维汀等的肿瘤靶标治疗的成功[1]。
除了理解和找出肿瘤产生和发展的遗传学机制外,肿瘤基因组学最主要的目的是为了开发肿瘤个性化治疗的方法。肿瘤的产生是由于 DNA 变异的累积。但这些变异是随机产生的,甚至在相同类型的肿瘤个体间变异的种类和组合都不相同。所以能够识别和定位病人个体的独特变异可能会提高肿瘤的治疗效果。
数位核型分析:又是另一种高分辨率、高通量量化样本里基因拷贝数的方法。将样本 DNA 利用限制酶剪切后的基因组片段,与 PET(英语:Paired-end tag) 相连、扩增之后再测序。将这些序列映射到参考基因组(英语:reference genome)即可量化基因组 DNA 增强或是删除的区域[9][10]。
在测序与表达数据量逐渐增大的现在,生物信息学的发展已成为关键。另外,在各种肿瘤基因已经被发现的现在,对于这些基因的功能描述与这些基因整体如何产生癌症表型的研究仍未完成。举例来说,检验肿瘤基因的转化能力[需要解释]即可确认这些肿瘤基因对于肿瘤形成有作用。另外,肿瘤细胞有各种 DNA 突变,找出哪些基因在肿瘤形成与发展的早期有关键作用也是件重要的研究工作。在这些基因中找到突变会是未来癌症诊断并找出治疗方法中最关键的步骤。
Strausberg R.L.; Simpson, Andrew J.G.; Old, Lloyd J.; Riggins, Gregory J.; et al. , (2004) Oncogenomics and the development of new cancer therapies. Nature. 2004, 429 (6990): 469–474. Bibcode:2004Natur.429..469S. PMID 15164073. doi:10.1038/nature02627. 引文格式1维护:显式使用等标签 (link)
Bardelli A., Velculescu V.E. Mutational analysis of gene families in human cancer. Current Opinion in Genetics & Development. 2005, 15 (1): 5–12. doi:10.1016/j.gde.2004.12.009.
Benvenuti S., Arena S., Bardelli A. Identification of cancer genes by mutational profiling of tumor genomes. Febs Letters. 2005, 579 (8): 1884–1890. PMID 15763568. doi:10.1016/j.febslet.2005.02.015.
Van , de Vijver M.J.; et al. , "A gene-expression signature as a predictor of survival in breast cancer. New England Journal of Medicine. 2002, 347 (25): 1999–2009. PMID 12490681. doi:10.1056/NEJMoa021967. 引文格式1维护:显式使用等标签 (link)
Hanash S.M. Operomics: Molecular analysis of tissues from DNA to RNA to protein. Clinical Chemistry and Laboratory Medicine. 2000, 38 (9): 805–813. doi:10.1515/CCLM.2000.116.
Kaelin W.G. The concept of synthetic lethality in the context of anticancer therapy. Nature Reviews Cancer. 2005, 5 (9): 689–698. PMID 16110319. doi:10.1038/nrc1691.
O'Connor M.J., Martin N.M.B., Smith G.C.M. Targeted cancer therapies based on the inhibition of DNA strand break repair. Oncogene. 2007, 26 (56): 7816–7824. PMID 18066095. doi:10.1038/sj.onc.1210879.
Samuels Y.; et al. , "High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004, 304 (5670): 554–554. PMID 15016963. doi:10.1126/science.1096502. 引文格式1维护:显式使用等标签 (link)
Hung, W.Y.; J.C. Lin; L.M. Lee; et al. Tandem duplication/triplication correlated with poly-cytosine stretch variation in human mitochondrial DNA D-loop region. Mutagenesis. 2008, 23 (2): 137–142. PMID 18252697. doi:10.1093/mutage/gen002.
Dani, M.A.; S.U. Dani; S.P. Lima; et al. Less ΔmtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation. Genet. Mol. Res. 2004, 3 (3): 395–409. PMID 15614730.
Ye, C.; X.O. Shu; W. Wen; et al. Quantitative analysis of mitochondrial DNA 4977-bp deletion in sporadic breast cancer and benign breast diseases. Breast Cancer Res. Treat. 2008, 108 (3): 427–434. PMID 17541740. doi:10.1007/s10549-007-9613-9.
Tseng, L.M.; P.H. Yin; C.W. Chi; et al. Mitochondrial DNA mutations and mitochondrial DNA depletion in breast cancer. Genes Chromosomes Cancer. 2006, 45 (7): 629–638. PMID 16568452. doi:10.1002/gcc.20326.
Zhu, W.; W. Qin; P. Bradley; A. Wessel; C.L. Puckett; E.R. Sauter. Mitochondrial DNA mutations in breast cancer tissue and in matched nipple aspirate fluid. Carcinogenesis. 2005, 26 (1): 145–152. PMID 15375011. doi:10.1093/carcin/bgh282.
Poetsch, M.; A. Petersmann; E. Lignitz; B. Kleist. Relationship between mitochondrial DNA instability, mitochondrial DNA large deletions, and nuclear microsatellite instability in head and neck squamous cell carcinomas. Diagn. Mol. Pathol. 2004, 13 (1): 26–32. PMID 15163006. doi:10.1097/00019606-200403000-00005.
Lee, H.C.; S.H. Li; J.C. Lin; C.C. Wu; D.C. Yeh; Y.H. Wei. Somatic mutations in the D-loop and decrease in the copy number of mitochondrial DNA in human hepatocellular carcinoma. Mutation Research. 2004, 547 (1–2): 71–78. PMID 15013701. doi:10.1016/j.mrfmmm.2003.12.011.
Kassauei, K.; N. Habbe; M.E. Mullendore; C.A. Karikari; A. Maitra; G. Feldmann. Mitochondrial DNA mutations in pancreatic cancer. Int. J. Gastrointest. Cancer. 2006, 37 (2–3): 57–64. PMID 17827523. doi:10.1007/s12029-007-0008-2.
Hung, W.Y.; C.W. Wu; P.H. Yin; et al. Somatic mutations in mitochondrial genome and their potential roles in the progression of human gastric cancer. Biochim. Biophys. Acta. 2010, 1800 (3): 264–270. ISBN 978-953-307-086-5. PMID 19527772. doi:10.5772/8630.
Gomez-Zaera, M.; J. Abril; L. Gonzalez; et al. Identification of somatic and germline mitochondrial DNA sequence variants in prostate cancer patients. Mutation Research. 2006, 595 (1–2): 42–51. PMID 16472830. doi:10.1016/j.mrfmmm.2005.10.012.
Ludwig, Joseph A.; Weinstein, John N. Biomarkers in Cancer Staging, Prognosis and Treatment Selection. Nature Reviews Cancer. 20 October 2005, 5 (11): 845–856. PMID 16239904. doi:10.1038/nrc1739.
Cancer Genome Project: an oncogenomic reference database from the Wellcome Trust Sanger Institute