Circulating tumor (ct)-DNA alterations in patients with testicular germ cell tumors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 415-415
Author(s):  
Archana Agarwal ◽  
Amin Nassar ◽  
Rebecca Nagy ◽  
Catherine Curran ◽  
Sarah Abou Alaiwi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Mutations ◽  
Demographic Data ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
The Usa ◽  
Evolution Of Resistance ◽  
Dna Alterations ◽  
Ctdna Analysis

415 Background: Testicular germ cell tumors (GCT) infrequently harbor somatic mutations. ctDNA assessment allows the noninvasive genomic profiling of malignancies and may assist with understanding molecular evolution of resistance. We report ctDNA profiling of patients (pts) with testicular GCTs. Methods: 40 patients (pts) with advanced testicular GCTs from multiple institutions in the USA that underwent ctDNA analysis using the Guardant (G)-360 platform were eligible and a total of 48 samples were collected. 36 pts had one sample, 3 pts had 2 samples, 1 pt had 6 samples. De-identified demographic data were collected in addition to data for ctDNA alterations. G360 employed a CLIA-certified ctDNA panel that assessed single nucleotide variant and copy number alterations in 68 to 73 genes for potentially actionable genomic alterations. Variants reported at least 3 times in the Catalogue of Somatic Mutations in Cancer (COSMIC) database or found in OncoKB were considered pathogenic. Results: Of 40 patients with testicular GCTs, 13pts (33%) were post systemic therapy. The median age was 36 years (range 20-61). 199 ctDNA alterations were detected in 35 patients (87.5%) across 41 genes. Among the 199 alterations, 102 were believed to be pathogenic and detectable in 26 samples from 25 pts (62.5) (%). The most common pathogenic somatic alterations were KRAS (n = 16/102, 16%), TP53 (n = 16/102, 16%), CCND2 (n = 9/102, 9%), CDK6 (n = 9/102, 9%), MET (n = 9/102, 9%), and RAF1 (n = 6/102, 6%). Conclusions: ctDNA alterations were frequently detected in resistant testicular GCTs and appear similar to alterations previously described in tumor tissue analyses of testicular GCTs. Given that ctDNA offers a non-invasive means of profiling tumor DNA, further development of this promising modality is warranted to study the evolution of resistance to cisplatin-based chemotherapy and new potentially actionable alterations.

Circulating tumor (ct)-DNA alterations in patients with testicular germ tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16063-e16063 ◽  
Author(s):  
Amin Nassar ◽  
Archana Agarwal ◽  
Rebecca Nagy ◽  
Catherine Curran ◽  
Sarah Abou Alaiwi ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Demographic Data ◽  
Germ Cell Tumors ◽  
The United States ◽  
Median Number ◽  
Genomic Alterations ◽  
Testicular Germ Cell ◽  
Dna Alterations ◽  
Ctdna Analysis ◽  
Serial Samples

e16063 Background: Testicular germ cell tumors (GCT) infrequently harbor somatic mutations. ctDNA assay allows the noninvasive genomic profiling of malignancies and may assist with understanding molecular evolution of resistance. To our knowledge, ctDNA genomic alterations observed in in testicular GCTs have not been heretofore described. We report ctDNA profiling of patients (pts) with testicular GCTs. Methods: 31 Pts with testicular GCTs from multiple institutions in the United States that underwent ctDNA analysis using the Guardant360 platform were eligible. Two patients had one serial ctDNA sample. De-identified demographic data were collected in addition to data for ctDNA alterations. Guardant360 is a CLIA-certified ctDNA panel that assesses single nucleotide variant and copy number alterations in 68 to 73 genes for potentially actionable genomic alterations. Variants reported at least 3 times in the Catalogue of Somatic Mutations in Cancer (COSMIC) database or found in OncoKB were considered pathogenic. Results: Of 31 patients with testicular GCTs, 162 ctDNA alterations were detected in 26 patients (84%) across 41 genes (Table). A median number of 3 alterations (range 1-19) was detected per sample. Among the 162 alterations, 88 were believed to be pathogenic and detectable in 20 patients (65%). 12/31 pts (39%) were documented to be post systemic therapy. The median age was 38 years (range 20-61). The most common pathogenic somatic alterations were KRAS (n = 12/88, 14%), CCND2 (n = 8/88, 9%), MET (n = 8/88, 9%), CDK6 (n = 7/88, 8%), TP53 (n = 6/88, 7%), and RAF1 (n = 5/88, 6%). In 2 patients with serial samples, 5 novel pathogenic alterations were detected in the second sample including FGFR2, APC, CDK6, RAF1, and MAPK1. Conclusions: ctDNA alterations were frequently detected in resistant testicular GCTs and appear similar to alterations previously described in tumor tissue analyses of testicular GCTs. Given that ctDNA offers a non-invasive means of profiling tumor DNA, further development of this promising modality is warranted to determine it's relevance in clinical practice. [Table: see text]

Sarcomatoid Yolk Sac Tumor Harbors Somatic Mutations That Are Otherwise Rare in Testicular Germ Cell Tumors

2022 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Andres M. Acosta ◽  
Khaleel I. Al-Obaidy ◽  
Lynette M. Sholl ◽  
Brendan C. Dickson ◽  
Neal I. Lindeman ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Mutations ◽  
Germ Cell Tumors ◽  
Yolk Sac ◽  
Yolk Sac Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

Serum Lactate Dehydrogenase Isoenzyme 1 and Relapse in Patients with Nonseminomatous Testicular Germ Cell Tumors Clinical Stage I

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Germ Cell ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Serum Lactate ◽  
Stage I ◽  
Serum Lactate Dehydrogenase ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dehydrogenase Isoenzyme

Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications

2018 ◽  
Vol 18 (10) ◽  
pp. 967-978 ◽  
Author(s):  
Katarina Kalavska ◽  
Vincenza Conteduca ◽  
Ugo De Giorgi ◽  
Michal Mego
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Cisplatin Resistance ◽  
Apoptotic Cell ◽  
Germ Cell Tumors ◽  
Treatment Resistance ◽  
Experimental Models ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Repair Capacity

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors’ biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

scholarly journals Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

2021 ◽  
pp. 1-7
Author(s):  
Pia Paffenholz ◽  
Tim Nestler ◽  
Yasmine Maatoug ◽  
Melanie von Brandenstein ◽  
Barbara Köditz ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Retroperitoneal Lymph Node Dissection ◽  
Advanced Tumor Stage ◽  
Testicular Germ Cell Tumors ◽  
Relapse Free Survival ◽  
Testicular Germ Cell ◽  
Free Survival ◽  
Advanced Tumor ◽  
The Impact

<b><i>Introduction:</i></b> The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. <b><i>Methods:</i></b> We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. <b><i>Results:</i></b> Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, <i>p</i> = 0.031), visceral metastases (58 vs. 32%, <i>p</i> = 0.015), and poor prognosis (<i>p</i> = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, <i>p</i> = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, <i>p</i> = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (<i>p</i> = 0.049) during a median follow-up of 36 months (10–115.5). <b><i>Conclusions:</i></b> The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

Management of residual masses in testicular germ cell tumors

2019 ◽  
Vol 19 (4) ◽  
pp. 291-300 ◽  
Author(s):  
Axel Heidenreich ◽  
Pia Paffenholz ◽  
Tim Nestler ◽  
David Pfister
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Residual Masses
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