Follicular lymphoma (FL) exhibits considerable variability in biological features and clinical trajectories across patients. To dissect the diversity of FL, we utilized a Bernoulli mixture model to identify genetic subtypes in 713 pre-treatment tumor tissue samples. Our analysis revealed the existence of five subtypes with unique genetic profiles that correlated with clinicopathological characteristics. The clusters were enriched in specific mutations as follows: CS (CREBBP and STAT6), TT (TNFAIP3 and TP53), GM (GNA13 and MEF2B), Q (quiescent, for low mutation burden), and AR (mutations of mTOR pathway-related genes). The subtype Q was enriched for patients with stage I disease and associated with a lower proliferative history than the other subtypes. The AR subtype was unique in its enrichment for IgM-expressing FL cases and was associated with advanced-stage and more than 4 nodal sites. The existence of subtypes was validated in an independent cohort of 418 samples from the GALLIUM trial. Notably, patients assigned to the TT subtype consistently experienced inferior progression-free survival when treated with immunochemotherapy. Our findings offer insight into core pathways distinctly linked with each FL cluster and are expected to be informative in the era of targeted therapies.
滤泡性淋巴瘤（FL）在生物学特征和临床病程方面存在显著的患间异质性。为解析这种异质性，我们利用伯努利混合模型对713例治疗前肿瘤组织样本进行基因亚型识别。分析结果显示存在五种具有独特遗传特征的亚型，这些特征与临床病理特征相关。各亚型富集的特定突变如下：CS型（CREBBP与STAT6突变）、TT型（TNFAIP3与TP53突变）、GM型（GNA13与MEF2B突变）、Q型（静息型，突变负荷较低）以及AR型（mTOR通路相关基因突变）。Q型亚型在Ⅰ期疾病患者中富集，且相比其他亚型具有更低的增殖活性病史。AR型亚型独特之处在于其在表达IgM的FL病例中富集，并与晚期疾病及超过4个淋巴结受累相关。这些亚型在GALLIUM试验的418例独立样本队列中得到验证。值得注意的是，在免疫化疗治疗中，归属于TT亚型的患者始终表现出较差的无进展生存期。本研究结果揭示了与各FL亚型明确相关的核心通路，预期可为靶向治疗时代提供重要参考信息。
肿瘤(癌症)患者之家