Identification of genetic subtypes in follicular lymphoma.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Shelton Victoria, Detroja Rajesh, Liu Ting, Isaev Keren, Silva Anjali, Passerini Verena, Bakhtiari Mehran, Calvente Lourdes, Hong Michael, He Michael Y, Modi Saloni, Hershenfeld Samantha A, Ludvigsen Maja, Madsen Charlotte, Hamilton-Dutoit Stephen, d'Amore Francesco Annibale, Brodtkorb Marianne, Johnson Nathalie A, Baetz Tara, LeBrun David, Tobin Josh W D, Gandhi Maher K, Mungall Andrew J, Xu Wei, Ben-Neriah Susana, Steidl Christian, Delabie Jan, Tremblay-LeMay Rosemarie, Jegede Opeyemi, Weigert Oliver, Kahl Brad, Evens Andrew M, Kridel Robert
Аннотация
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.