TP53 and PTEN Mutations Were Shared in Concurrent Germ Cell Tumor and Acute Megakaryoblastic Leukemia

Abstract

Background: The occurrence of a mediastinal germ cell tumor (GCT) and hematological malignancy in the same patient is very rare. Due to its rarity, there have been only two reports of the concurrent cases undergoing detailed genetic analysis with whole-exome sequencing (WES), and the possible clonal relationship between the both tumors remained not fully elucidated. Methods: We performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results: 16 somatic mutations were detected in the mediastinal GCT sample and 18 somatic mutations in the AML sample. Mutations in nine genes, including TP53 and PTEN both known as tumor suppressor genes, were shared in both tumors. Conclusions: All in our case and in the previous two cases with concurrent mediastinal GCT and AML undergoing with whole-exome sequencing analysis, TP53 and PTEN mutations were commonly shared in both tumors. These data not only suggest that these tumors share a common founding clone, but also indicate that associated mediastinal GCT and AML harboring TP53 and PTEN mutations represent a unique biological entity.

Mediastinal Germ Cell Tumor and Acute Megakaryoblastic Leukemia With Co-occurring KRAS Mutation and Complex Cytogenetics

“…We detected co-occurring mutations in TP53 and PTEN similar to previous reports. [12][13][14] The TP53 p. Leu257Pro mutation is a reported pathogenic variant in cancer databases. CG-LOH of 17p13 was also observed consistent with the high VAF and indicative of wild-type TP53 loss in both malignancies consistent with the observed strong and diffuse immunohistochemical TP53 staining.…”

“…10,11 More recently, next-generation sequencing (NGS) analyses identified co-occurring somatic mutations in Tumor Protein P53(TP53) and Phosphatase And Tensin Homolog (PTEN) as recurrent molecular features. [12][13][14] We report a case of an adolescent male with mediastinal NSGCT exhibiting diverse areas of high-grade sarcomatous differentiation and onset of AMKL approximately 4 months after the diagnosis of NSGCT. Conventional karyotyping and cancer microarray analysis revealed similar complex cytogenomic abnormalities.…”

“…10 , 11 More recently, next-generation sequencing (NGS) analyses identified co-occurring somatic mutations in Tumor Protein P53(TP53) and Phosphatase And Tensin Homolog (PTEN) as recurrent molecular features. 12–14…”