文章：

胃肠道间质瘤：起源和分子肿瘤学

Gastrointestinal stromal tumours: origin and molecular oncology

原文发布日期：2011-11-17

DOI: 10.1038/nrc3143

类型: Review Article

开放获取: 否

要点：

1. Gastrointestinal stromal tumours (GISTs) are a family of tumours thought to arise from the interstitial cells of Cajal in the gastrointestinal tract. Recently, the putative stem and progenitor cells for GISTs have been identified.
2. Most GISTs have oncogenic mutations in either KIT or platelet-derived growth factor receptor-α (PDGFRA), and targeting these mutant proteins with kinase inhibitors is effective in patients with advanced disease. There is substantial evidence that these mutations are pathogenetic for the initiation of GISTs.
3. GISTs lacking KIT or PDGFRA mutations (known as wild-type GISTs) are a heterogeneous group, of which some have alterations in BRAF, RAS or in the genes of the succinate dehydrogenase complex.
4. Classification of GISTs on the basis of molecular defects is relevant to the clinical management of patients. Notably, the response to kinase inhibitor therapy is influenced by the primary kinase genotype.
5. Secondary mutations in KIT or PDGFRA eventually lead to drug resistance in most patients.
6. A subpopulation of GIST cells with stem cell-like characteristics may be less sensitive to kinase inhibitors, providing the seed for drug resistance.

要点翻译：

1. 胃肠道间质瘤（GIST）是一类被认为起源于胃肠道卡哈尔间质细胞的肿瘤家族。近期，GIST的推定干细胞与祖细胞已被识别。
2. 大多数GIST存在KIT或血小板衍生生长因子受体α（PDGFRA）的致癌突变，使用激酶抑制剂靶向这些突变蛋白对晚期疾病患者具有治疗效果。充分证据表明这些突变对GIST的起始发展具有致病作用。
3. 缺乏KIT或PDGFRA突变的GIST（称为野生型GIST）是一个异质性群体，其中部分存在BRAF、RAS或琥珀酸脱氢酶复合体基因的改变。
4. 基于分子缺陷的GIST分类与患者临床管理密切相关。值得注意的是，激酶抑制剂治疗的疗效受到原发性激酶基因型的影响。
5. 大多数患者中，KIT或PDGFRA的继发性突变最终会导致耐药性。
6. 具有干细胞样特征的GIST细胞亚群可能对激酶抑制剂敏感性较低，这为耐药性提供了种子细胞。

英文摘要：

Gastrointestinal stromal tumours (GISTs) are a paradigm for the development of personalized treatment for cancer patients. The nearly simultaneous discovery of a biomarker that is reflective of their origin and the presence of gain-of-function kinase mutations in these tumours set the stage for more accurate diagnosis and the development of kinase inhibitor therapy. Subsequent studies of genotype and phenotype have led to a molecular classification of GIST and to treatment optimization on the basis of molecular subtype. The study of drug-resistant tumours has advanced our understanding of kinase biology, enabling the development of novel kinase inhibitors. Further improvements in GIST treatment may require targeting GIST stem cell populations and/or additional genomic events.

摘要翻译： 

胃肠道间质瘤（GIST）是个体化癌症治疗发展的范例。对其起源具有提示作用的生物标志物的发现，与这些肿瘤中存在激酶激活突变的现象几乎同时出现，为更准确的诊断和激酶抑制剂治疗的开发奠定了基础。随后对基因型与表型的研究，推动了GIST的分子分型，并实现了基于分子亚型的治疗优化。对耐药肿瘤的研究深化了我们对激酶生物学的理解，促进了新型激酶抑制剂的开发。GIST治疗的进一步改善，可能需要靶向GIST干细胞群体和/或其他基因组事件。

原文链接：

Gastrointestinal stromal tumours: origin and molecular oncology