Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, British Columbia, Canada.
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei tumori, Milan, Italy.
Oncologist. 2022 Nov 3;27(11):e912-e915. doi: 10.1093/oncolo/oyac197.
Primary mediastinal nonseminoma germ cell tumors (PMNSGCT) are a subgroup of nonseminoma germ cell tumors (GCT) with poor prognosis. In this study, PMNSGCT-specific genomic landscape was analyzed and correlated with clinical outcomes.
DNA was extracted and sequenced from 28 archival tumor tissue of patients with mediastinal GCT (3 seminoma and 25 nonseminoma). Overall survival (OS) and association with gene alterations were estimated using the Kaplan-Meier and univariate Cox regression methods.
Three patients (11%) had a karyotype XXY, 17/28 (61%) tumor samples presented chromosome 12p amplification. Somatic mutations were detected in 19/28 (68%) samples. The most frequently mutated genes were: TP53 (13/28; 46%), KIT (5/28; 18%), and KRAS (5/28; 18%). Deleterious TP53 alterations were associated with significantly reduced overall survival (HR: 7.16; P = .012).
TP53 alterations are common in PMNSGCT and are associated with reduced overall survival, potentially underlying the poor sensitivity to chemotherapy observed in these patients.
原发性纵隔非精原细胞瘤生殖细胞肿瘤（PMNSGCT）是预后较差的非精原细胞瘤生殖细胞肿瘤（GCT）的一个亚组。本研究分析了 PMNSGCT 的特异性基因组图谱，并将其与临床结果相关联。
从 3 例纵隔 GCT（3 例精原细胞瘤和 25 例非精原细胞瘤）的 28 例存档肿瘤组织中提取并测序 DNA。使用 Kaplan-Meier 和单变量 Cox 回归方法估计总生存期（OS）和与基因改变的关联。
3 名患者（11%）存在性染色体 XXY，28 例肿瘤样本中有 17/28（61%）存在 12p 染色体扩增。在 28 例样本中检测到 19/28（68%）的体细胞突变。最常突变的基因是：TP53（13/28；46%）、KIT（5/28；18%）和 KRAS（5/28；18%）。有害性的 TP53 改变与总生存期明显缩短相关（HR：7.16；P=0.012）。
TP53 改变在 PMNSGCT 中很常见，与总生存期缩短相关，可能是这些患者对化疗敏感性降低的原因。
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