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White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41467-020-14310-3 Alessandro Leal 1 , Nicole C T van Grieken 2 , Doreen N Palsgrove 1 , Jillian Phallen 1 , Jamie E Medina 1 , Carolyn Hruban 1 , Mark A M Broeckaert 2 , Valsamo Anagnostou 1 , Vilmos Adleff 1 , Daniel C Bruhm 1 , Jenna V Canzoniero 3 , Jacob Fiksel 1 , Marianne Nordsmark 4 , Fabienne A R M Warmerdam 5 , Henk M W Verheul 6 , Dick Johan van Spronsen 7 , Laurens V Beerepoot 8 , Maud M Geenen 9 , Johanneke E A Portielje 10, 11 , Edwin P M Jansen 12 , Johanna van Sandick 13 , Elma Meershoek-Klein Kranenbarg 14 , Hanneke W M van Laarhoven 15 , Donald L van der Peet 16 , Cornelis J H van de Velde 14 , Marcel Verheij 12 , Remond Fijneman 17 , Robert B Scharpf 1 , Gerrit A Meijer 17 , Annemieke Cats 18 , Victor E Velculescu 1
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41467-020-14310-3 Alessandro Leal 1 , Nicole C T van Grieken 2 , Doreen N Palsgrove 1 , Jillian Phallen 1 , Jamie E Medina 1 , Carolyn Hruban 1 , Mark A M Broeckaert 2 , Valsamo Anagnostou 1 , Vilmos Adleff 1 , Daniel C Bruhm 1 , Jenna V Canzoniero 3 , Jacob Fiksel 1 , Marianne Nordsmark 4 , Fabienne A R M Warmerdam 5 , Henk M W Verheul 6 , Dick Johan van Spronsen 7 , Laurens V Beerepoot 8 , Maud M Geenen 9 , Johanneke E A Portielje 10, 11 , Edwin P M Jansen 12 , Johanna van Sandick 13 , Elma Meershoek-Klein Kranenbarg 14 , Hanneke W M van Laarhoven 15 , Donald L van der Peet 16 , Cornelis J H van de Velde 14 , Marcel Verheij 12 , Remond Fijneman 17 , Robert B Scharpf 1 , Gerrit A Meijer 17 , Annemieke Cats 18 , Victor E Velculescu 1
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Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
中文翻译：
白细胞和无细胞DNA分析可检测胃癌中的残留疾病。
液体活检为手术后检测无细胞DNA（cfDNA）中的残留疾病提供了新的机会，但可能通过鉴定克隆性造血所引起的改变而混淆。在这里，我们通过对来自同一患者的匹配的cfDNA和白细胞进行超灵敏的靶向测序分析，来鉴定循环肿瘤来源的DNA（ctDNA）的变化。我们采用这种方法来分析CRITICS试验中患者的样本，该试验是可手术胃癌患者围手术期治疗的III期随机对照研究。在滤除匹配的白细胞的变化后，在符合多模式治疗条件的患者的术前治疗和手术后九周内分析时，ctDNA的存在可预测复发。
更新日期：2020-01-27
中文翻译：
白细胞和无细胞DNA分析可检测胃癌中的残留疾病。
液体活检为手术后检测无细胞DNA（cfDNA）中的残留疾病提供了新的机会，但可能通过鉴定克隆性造血所引起的改变而混淆。在这里，我们通过对来自同一患者的匹配的cfDNA和白细胞进行超灵敏的靶向测序分析，来鉴定循环肿瘤来源的DNA（ctDNA）的变化。我们采用这种方法来分析CRITICS试验中患者的样本，该试验是可手术胃癌患者围手术期治疗的III期随机对照研究。在滤除匹配的白细胞的变化后，在符合多模式治疗条件的患者的术前治疗和手术后九周内分析时，ctDNA的存在可预测复发。
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