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治疗压力下转移性癌症基因组的演化有限
作者:小柯机器人 发布时间:2021/8/13 16:36:53

荷兰癌症研究所Emile E. Voest课题组发现,治疗压力下转移性癌症基因组的演化有限。这一研究成果于2021年8月9日在线发表在国际学术期刊《自然—医学》上。

研究人员表示,基因组分析对于确定转移性癌症患者的治疗方案至关重要,但目前仍不清楚在疾病的治疗过程中应该多长时间重复一次这种程序。

为了解决这个问题,研究人员分析了250对活检的全基因组测序(WGS)数据,这些数据是在231名患有各种代表性转移性实体恶性肿瘤成年患者的治疗过程中纵向收集的。在活检间隔期间(中位数,6.4个月),患者接受了一种或多种(主要是)标准护理(SOC)治疗,所有主要的治疗方式都有广泛代表性。在23%和72%的活检中,可以分别确定SOC生物标志物和临床试验的生物标志物。对于SOC基因组生物标志物,研究人员观察到99%的第一和第二次活检完全一致。在第一次活检中发现的219个用于临床试验的生物标志物中,研究人员在后续活检中发现了94%。

此外,在91%的患者中,第二次WGS分析并没有发现额外的生物标志物可被用于临床试验的招募。当考虑到小分子抑制剂或荷尔蒙疗法的特定基因时,更频繁的基因组演化(分别为21%和22%的病例)被观察到。总之,这些数据表明,经治疗后转移瘤基因组的演化是有限的。对转移性活检进行一次WGS分析一般就足以确定SOC基因组生物标志物,并确定治疗机会。

附:英文原文

Title: Limited evolution of the actionable metastatic cancer genome under therapeutic pressure

Author: van de Haar, Joris, Hoes, Louisa R., Roepman, Paul, Lolkema, Martijn P., Verheul, Henk M. W., Gelderblom, Hans, de Langen, Adrianus J., Smit, Egbert F., Cuppen, Edwin, Wessels, Lodewyk F. A., Voest, Emile E.

Issue&Volume: 2021-08-09

Abstract: Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.

DOI: 10.1038/s41591-021-01448-w

Source: https://www.nature.com/articles/s41591-021-01448-w

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex