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Germ cell tumors and associated hematologic malignancies evolve from a common shared precursor.

ABSTRACT: Germ cell tumors (GCTs) are the most common cancer in men between the ages of 15 and 40. Although most patients are cured, those with disease arising in the mediastinum have distinctly poor outcomes. One in every 17 patients with primary mediastinal nonseminomatous GCTs develop an incurable hematologic malignancy and prior data intriguingly suggest a clonal relationship exists between hematologic malignancies and GCTs in these cases. To date, however, the precise clonal relationship between GCTs and the diverse additional somatic malignancies arising in such individuals have not been determined. Here, we traced the clonal evolution and characterized the genetic features of each neoplasm from a cohort of 15 patients with GCTs and associated hematologic malignancies. We discovered that GCTs and hematologic malignancies developing in such individuals evolved from a common shared precursor, nearly all of which harbored allelically imbalanced p53 and/or RAS pathway mutations. Hematologic malignancies arising in this setting genetically resembled mediastinal GCTs rather than de novo myeloid neoplasms. Our findings argue that this scenario represents a unique clinical syndrome, distinct from de novo GCTs or hematologic malignancies, initiated by an ancestral precursor that gives rise to the parallel evolution of GCTs and blood cancers in these patients.

SUBMITTER: Taylor J

PROVIDER: S-EPMC7685753 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Germ cell tumors and associated hematologic malignancies evolve from a common shared precursor.

Taylor Justin J Donoghue Mark Ta MT Ho Caleb C Petrova-Drus Kseniya K Al-Ahmadie Hikmat A HA Funt Samuel A SA Zhang Yanming Y Aypar Umut U Rao Pavitra P Chavan Shweta S SS Haddadin Michael M Tamari Roni R Giralt Sergio S Tallman Martin S MS Rampal Raajit K RK Baez Priscilla P Kappagantula Rajya R Kosuri Satyajit S Dogan Ahmet A Tickoo Satish K SK Reuter Victor E VE Bosl George J GJ Iacobuzio-Donahue Christine A CA Solit David B DB Taylor Barry S BS Feldman Darren R DR Abdel-Wahab Omar O

The Journal of clinical investigation 20201201 12

Germ cell tumors (GCTs) are the most common cancer in men between the ages of 15 and 40. Although most patients are cured, those with disease arising in the mediastinum have distinctly poor outcomes. One in every 17 patients with primary mediastinal nonseminomatous GCTs develop an incurable hematologic malignancy and prior data intriguingly suggest a clonal relationship exists between hematologic malignancies and GCTs in these cases. To date, however, the precise clonal relationship between GCTs ...[more]

PMID: 32897884

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Dataset Information

Germ cell tumors and associated hematologic malignancies evolve from a common shared precursor.

Publications

Germ cell tumors and associated hematologic malignancies evolve from a common shared precursor.

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