Hematologic Malignancies Arising in Patients with Germ Cell Tumors: Secondary Somatic Differentiation of Hematopoietic Malignancies from Germ Cell Precursors

Genomic analyses have recently illuminated our understanding of therapy-associated myeloid neoplasms in patients receiving therapy for other cancers. One of the most intriguing relationships between solid tumors and myeloid neoplasms involves a unique clinical entity of patients with germ cell tumors (GCT) and myeloid neoplasms. One in 17 patients with primary mediastinal germ cell tumor (PMGCT) develops a hematologic malignancy (most commonly AML, MDS, or histiocytosis) and the median survival in such patients is poor at only 5 months. Intriguingly, the presence of isochromosome 12p [i(12p)], a clonal marker common to GCTs but absent in de novo myeloid neoplasms, has been demonstrated as shared across GCTs and myeloid neoplasms in such individuals. While these data suggest a clonal relationship between the two, the exact nature of the shared origin is unknown. There are two competing hypotheses to explain this: (1) an embryonic progenitor with the capacity to differentiate into germ cell and hematopoietic lineages harbors the initiating genetic alterations and drives development of both malignancies or (2) the leukemia is derived directly from GCTs with the capacity to differentiate into hematopoietic lineages. To trace the clonal evolution of these seemingly unrelated cancer types and identify recurrent genomic lesions in leukemias present in GCT patients, we applied whole exome sequencing (WES), targeted genomic analyses, and/or RNA-seq to leukemias, GCTs, and germline DNA...
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis I Source Type: research