滤泡性淋巴瘤（FL）在不同患者的生物学特征和临床轨迹上表现出相当大的变异性。为了剖析 FL 的多样性，我们利用伯努利混合模型来识别 713 个治疗前肿瘤组织样本中的遗传亚型。我们的分析揭示了存在五种具有与临床病理特征相关的独特遗传图谱的亚型。这些簇富含以下特定突变：CS（CREBBP 和 STAT6）、TT（TNFAIP3 和 TP53）、GM（GNA13 和 MEF2B）、Q（静止，低突变负荷）和 AR（mTOR 通路相关突变）基因）。 Q 亚型在 I 期疾病患者中丰富，并且与其他亚型相比具有较低的增殖史。 AR 亚型在表达 IgM 的 FL 病例中具有独特性，并且与晚期和超过 4 个淋巴结部位相关。 GALLIUM 试验的 418 个样本的独立队列验证了亚型的存在。值得注意的是，分配给 TT 亚型的患者在接受免疫化疗治疗时始终经历较差的无进展生存期。我们的研究结果提供了对与每个 FL 簇明显相关的核心途径的深入了解，预计将在靶向治疗时代提供信息。© 2024。作者。

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.© 2024. The Author(s).