Sarkozy Clémentine, Huet Sarah, Carlton Victoria E H, Fabiani Bettina, Delmer Alain, Jardin Fabrice, Delfau-Larue Marie-Helene, Hacini Maya, Ribrag Vincent, Guidez Stéphanie, Faham Malek, Salles Gilles
Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Service d'Hématologie, 69495 Pierre Bénite Cedex, France.
NSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux Lyon-1, 69495 Pierre Bénite Cedex, France.
Oncotarget. 2017 Jan 31;8(5):8765-8774. doi: 10.18632/oncotarget.14448.
Recent advances in next-generation sequencing (NGS) have enabled the quantitation of circulating tumour DNA (ctDNA) encoding the clonal rearranged V(D)J immunoglobulin locus. We aimed to evaluate the clonal heterogeneity of follicular lymphoma (FL) in the tumour and the plasma at diagnosis and to assess the prognostic value of the ctDNA level. Plasma samples at diagnosis were available for 34 patients registered in the PRIMA trial (NCT00140582). One tumour clonotype or more could be detected for 29 (85%) and 25 (74%) patients, respectively, in the tumour or plasma samples. In 18 patients, several subclones were detected in the tumour (2 to 71 subclones/cases) and/or in the plasma (2 to 20 subclones/cases). In more than half of the cases, the distribution of subclones differed between the tumour and plasma samples, reflecting high clonal heterogeneity and diversity in lymphoma subclone dissemination. In multivariate analysis, a high level of ctDNA was the only independent factor associated with patients' progression-free survival (HR 4, IC 95 (1.1-37), p=.039). In conclusion, an NGS-based immunosequencing method reveals the marked clonal heterogeneity of follicular lymphoma in patients with FL, and quantification of ctDNA at diagnosis represents a potential powerful prognostic biomarker that needs to be investigated in larger cohorts.
新一代测序（NGS）技术的最新进展使得对编码克隆重排V（D）J免疫球蛋白基因座的循环肿瘤DNA（ctDNA）进行定量分析成为可能。我们旨在评估滤泡性淋巴瘤（FL）在诊断时肿瘤组织和血浆中的克隆异质性，并评估ctDNA水平的预后价值。PRIMA试验（NCT00140582）登记的34例患者在诊断时可获取血浆样本。在肿瘤样本和血浆样本中，分别有29例（85%）和25例（74%）患者可检测到一种或更多种肿瘤克隆型。18例患者的肿瘤组织（2至71个亚克隆/病例）和/或血浆中（2至20个亚克隆/病例）检测到多个亚克隆。在超过半数的病例中，肿瘤组织和血浆样本中亚克隆的分布不同，反映出淋巴瘤亚克隆播散中高度的克隆异质性和多样性。多因素分析中，ctDNA高水平是与患者无进展生存期相关的唯一独立因素（HR 4，95%CI（1.1 - 37），p = 0.039）。总之，基于NGS的免疫测序方法揭示了FL患者滤泡性淋巴瘤显著的克隆异质性，诊断时ctDNA定量分析代表一种潜在的强大预后生物标志物，需要在更大队列中进行研究。
