PDF(Pubmed)
Abstract：
UNASSIGNED: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center.
UNASSIGNED: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test.
UNASSIGNED: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable.
UNASSIGNED: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.
UNASSIGNED: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test.
UNASSIGNED: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable.
UNASSIGNED: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.
摘要：
睾丸生殖细胞瘤(TGCT)是年轻成年男性中最常见的癌症。TGCT的组织病理学是多种多样的，和基因组改变的频率，以及它们的预后作用，在很大程度上仍未探索。在这里，我们评估了来自单个参考癌症中心的一系列TGCT中的15个驱动基因组的突变谱和KRAS拷贝数变异.
■一项由97名TGCT患者组成的队列，在Barretos癌症医院确诊,进行了评估。应用Real-timePCR检测51例KRAS基因拷贝数变异(CNV),在65例患者中使用TruSight肿瘤15（Illumina）组（TST15）进行突变分析。使用单变量分析来比较样品类别与突变频率的关系。采用Kaplan-Meier法和对数秩检验进行生存分析。
■KRAS拷贝数增加是TGCT中非常常见的事件（80.4%），与没有KRAS拷贝数增加的组相比，预后较差（10y-OS，90%vs.81.5%,p=0.048)。在65例TGCT病例中，在该小组的15个基因中的11个中鉴定出不同的变体，TP53基因是突变最多的驱动基因(27.7%)。在KIT等基因中也检测到变异，KRAS,PDGFRA,EGFR,BRAF,RET,NRAS,PIK3CA,MET,和ERBB2，其中一些可能有针对性。
■尽管结合协作网络的更大研究可能会揭示TGCT的分子格局，我们的研究结果揭示了可操作变异在临床管理中应用靶向治疗的潜力.
■一项由97名TGCT患者组成的队列，在Barretos癌症医院确诊,进行了评估。应用Real-timePCR检测51例KRAS基因拷贝数变异(CNV),在65例患者中使用TruSight肿瘤15（Illumina）组（TST15）进行突变分析。使用单变量分析来比较样品类别与突变频率的关系。采用Kaplan-Meier法和对数秩检验进行生存分析。
■KRAS拷贝数增加是TGCT中非常常见的事件（80.4%），与没有KRAS拷贝数增加的组相比，预后较差（10y-OS，90%vs.81.5%,p=0.048)。在65例TGCT病例中，在该小组的15个基因中的11个中鉴定出不同的变体，TP53基因是突变最多的驱动基因(27.7%)。在KIT等基因中也检测到变异，KRAS,PDGFRA,EGFR,BRAF,RET,NRAS,PIK3CA,MET,和ERBB2，其中一些可能有针对性。
■尽管结合协作网络的更大研究可能会揭示TGCT的分子格局，我们的研究结果揭示了可操作变异在临床管理中应用靶向治疗的潜力.
