Laboratoire de Génomique Cellulaire des Cancers, INSERM U985 and Molecular Pathology, Biopathology Department, Institut de Cancérologie Gustave Roussy, 39 rue Camille Desmoulins, 94805 Paris-Villejuif Cedex, France.
Mol Oncol. 2010 Aug;4(4):309-22. doi: 10.1016/j.molonc.2010.06.003. Epub 2010 Jun 11.
The role of acquired chromosomal rearrangements in oncogenesis (cytogenomics) and tumor progression is now well established. These alterations are multiple and diverse and the products of these rearranged genes play an essential role in the transformation and growth of cancer cells. The validity of this assumption is demonstrated by the development of specific inhibitors or antibodies that eliminate tumoral cells by targeting some of these changes. Imatinib, an inhibitor of the tyrosine kinase ABL, the prototype of these targeting drugs, is yielding complete remissions in most CML patients. Knowledge of chromosomal abnormalities is becoming an essential contribution to the diagnosis and prognosis of cancers but also for monitoring minimal residual disease or relapse. The concept of the "cytogenetic uniqueness" of each cancer has resulted in personalized treatment. This investigation will expound upon, besides the recurrent genomic alterations, the numerous products of perverted Darwinian selection at the cellular level.
获得性染色体重排在肿瘤发生(细胞遗传学)和肿瘤进展中的作用现在已经得到充分证实。这些改变是多样的,这些重排基因的产物在癌细胞的转化和生长中起着至关重要的作用。这一假设的有效性通过开发特异性抑制剂或抗体得到了证明,这些抑制剂或抗体通过靶向这些改变中的某些来消除肿瘤细胞。伊马替尼是酪氨酸激酶 ABL 的抑制剂,是这些靶向药物的原型,它使大多数 CML 患者获得完全缓解。对染色体异常的认识已成为癌症诊断和预后的重要贡献,也有助于监测微小残留疾病或复发。“每个癌症的细胞遗传学独特性”的概念导致了个性化治疗。除了反复出现的基因组改变外,本研究还将阐述在细胞水平上发生的众多被歪曲的达尔文选择产物。