A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia
| Autor: | Christopher A. Miller, Ian S. Hagemann, Peter Westervelt, Obi L. Griffith, Vincent Magrini, Lukas D. Wartman, Peter A. Riedell, Michelle O'Laughlin, Bradley A. Ozenberger, Malachi Griffith, Charles Lu, Eric J. Duncavage, Ryan Demeter |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0303 health sciences
Mediastinal germ cell tumor Myeloid leukemia General Medicine Biology medicine.disease Somatic evolution in cancer neoplasm of the genitourinary tract FANCA 3. Good health hematological neoplasm 03 medical and health sciences Acute megakaryoblastic leukemia 0302 clinical medicine Fanconi anemia 030220 oncology & carcinogenesis hemic and lymphatic diseases medicine Cancer research biology.protein PTEN Exome 030304 developmental biology Research Article |
| Zdroj: | Cold Spring Harbor Molecular Case Studies |
| ISSN: | 2373-2873 2373-2865 |
| Popis: | We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data. |
| Databáze: | OpenAIRE |
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