Sawa Yun Cheng, Jia Liwei, Krause Harris, Meagher Margaret, Millard Frederick, Elliott Andrew, Lafin John T, Jamieson Christina, Antonarakis Emmanuel S, D'Souza Anishka, Giannikou Krinio, Amatruda James F, Daneshmand Siamak, McKay Rana R, Oberley Matthew, Nabhan Chadi, Bagrodia Aditya
Department of Urology, University of California San Diego, La Jolla, CA, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
NPJ Precis Oncol. 2024 Nov 2;8(1):249. doi: 10.1038/s41698-024-00727-2.
We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic germ cell tumors (GCTs; N = 138) to uncover factors that drive cisplatin resistance. Prevalence was calculated for platinum-resistant alterations (PRAs; KRAS, TP53, and KIT mutations, and MDM2 amplification) and high copy number amplifications (CNA ≥ 6 copies). Tumors were designated as chemo-naïve (PreC, N = 66) or post-chemotherapy (PostC, N = 17). A transcriptomic signature associated with platinum sensitivity (PSS, high suggests increased sensitivity) was applied. KIT mutations were observed in 14.5% of primary versus 1.8% of met and 0% of lymph. TP53 mutations were identified in 10% of primary GCTs versus 17% of met and 16.7% of lymph. MDM2 CNAs were similar between sites. PRA-positive PreC GCTs had significantly lower average PSS scores compared to PRA-negative tumors. Lower PSS scores in chemo-naïve tumors were associated with PRAs, suggesting a potential mechanism for platinum resistance.
我们试图评估原发性和转移性生殖细胞肿瘤（GCT；N = 138）的基因组和转录组图谱，以揭示驱动顺铂耐药的因素。计算铂耐药性改变（PRA；KRAS、TP53和KIT突变以及MDM2扩增）和高拷贝数扩增（CNA≥6拷贝）的发生率。肿瘤被指定为初治（PreC，N = 66）或化疗后（PostC，N = 17）。应用与铂敏感性相关的转录组特征（PSS，高分表明敏感性增加）。在14.5%的原发性肿瘤中观察到KIT突变，而在转移性肿瘤中为1.8%，在淋巴瘤中为0%。在10%的原发性GCT中鉴定出TP53突变，而在转移性肿瘤中为17%，在淋巴瘤中为16.7%。各部位之间MDM2的拷贝数改变相似。与PRA阴性肿瘤相比，PRA阳性的初治GCT的平均PSS评分显著更低。初治肿瘤中较低的PSS评分与PRA相关，提示铂耐药的一种潜在机制。
