The Landmark Discovery That Paved the Way to a Mechanistic Understanding of P53 Gain of Function and Personalized Medicine.
The Landmark Discovery That Paved the Way to a Mechanistic Understanding of P53 Gain of Function and Personalized Medicine.
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这一具有里程碑意义的发现为理解 P53 功能获得和个性化医疗的机制铺平了道路。
DOI：
10.1158/0008-5472.can-21-2382
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发表时间：
2021
期刊：
影响因子：
11.2
通讯作者：
Flores,ElsaR
中科院分区：
文献类型：
--
作者：
Napoli,Marco;Deshpande,AvaniA;Flores,ElsaR
1990 年，贝克及其同事在癌症研究中报告了他们的开创性发现，重点关注从腺瘤到结肠癌的转变。通过对 58 个结直肠肿瘤（25 个腺瘤和 33 个癌）中的 TP53 基因座进行测序并测量其等位基因缺失，他们发现这种转变需要一个 TP53 等位基因的丢失和另一个 TP53 等位基因的突变。在这里，我们讨论这一具有里程碑意义的发现如何为 p53 突变提供新的认识，促进新型小鼠模型的产生，最终证明这些结果所提出的突变 p53 功能获得假说。最后，我们评估了癌症进展的 Vogelstein 模型对癌症生物学和癌症护理的许多方面的影响，包括肿瘤进化的特征和对治疗的反应，以及它如何最终促进早期检测筛查和个性化医疗的广泛采用。参见 Baker 及其同事的相关文章，Cancer Res 1990;50:7717–22
In 1990, Baker and colleagues reported their seminal findings inCancer Researchfocusing on the transition from adenoma to carcinoma of the colon. By sequencing theTP53locus in 58 colorectal tumors (25 adenomas and 33 carcinomas) and measuring its allelic deletions, they discovered that this transition requires the loss of oneTP53allele and the mutation of the other one. Here, we discuss how this landmark discovery shed a new light on p53 mutations, prompting the generation of novel mouse models that definitively proved the mutant p53 gain-of-function hypothesis suggested by these results. Finally, we evaluate the implications that the Vogelstein model of cancer progression had on numerous aspects of cancer biology and cancer care, including the characterization of tumor evolution and the response to therapy, and how it ultimately contributed to the wider adoption of early detection screenings and personalized medicine.See related article by Baker and colleagues, Cancer Res 1990;50:7717–22