小柯机器人

澳大利亚墨尔本大学David D. L. Bowtell等研究人员合作揭示高级别浆液性卵巢癌长期生存者的基因组和免疫状况。这一研究成果于2022年12月1日在线发表在国际学术期刊《自然—遗传学》上。

研究人员使用全基因组测序、转录组和甲基组分析了60名诊断后存活超过10年的晚期高级别浆液性卵巢癌（HGSC）患者的原发肿瘤样本，将这些数据与66名短期或中度存活者进行比较。长期存活者的肿瘤更有可能在与DNA修复有关的基因中出现多种改变，以及更频繁的体细胞变异，导致预测的新抗原负荷增加。患者根据基因组和免疫细胞的特征分为生存组，包括三个具有明显不同结果的BRCA1改变的患者亚组。种系和体系基因改变的特定组合、肿瘤细胞表型和不同的免疫反应似乎有助于HGSC的长期生存。

据介绍，在所有晚期HGSC患者中，只有不到一半的人在诊断后存活超过5年，但那些存活时间特别长的人可以提供对肿瘤生物学和治疗方法的见解。

附：英文原文

Title: The genomic and immune landscape of long-term survivors of high-grade serous ovarian cancer

Author: Garsed, Dale W., Pandey, Ahwan, Fereday, Sian, Kennedy, Catherine J., Takahashi, Kazuaki, Alsop, Kathryn, Hamilton, Phineas T., Hendley, Joy, Chiew, Yoke-Eng, Traficante, Nadia, Provan, Pamela, Ariyaratne, Dinuka, Au-Yeung, George, Bateman, Nicholas W., Bowes, Leanne, Brand, Alison, Christie, Elizabeth L., Cunningham, Julie M., Friedlander, Michael, Grout, Bronwyn, Harnett, Paul, Hung, Jillian, McCauley, Bryan, McNally, Orla, Piskorz, Anna M., Saner, Flurina A. M., Vierkant, Robert A., Wang, Chen, Winham, Stacey J., Pharoah, Paul D. P., Brenton, James D., Conrads, Thomas P., Maxwell, George L., Ramus, Susan J., Pearce, Celeste Leigh, Pike, Malcolm C., Nelson, Brad H., Goode, Ellen L., DeFazio, Anna, Bowtell, David D. L.

Issue&Volume: 2022-12-01

Abstract: Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1 alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes and differential immune responses appear to contribute to long-term survival in HGSC.

DOI: 10.1038/s41588-022-01230-9

Source: https://www.nature.com/articles/s41588-022-01230-9

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex