TP53 and PTEN mutations were shared in concurrent germ cell tumor and acute megakaryoblastic leukemia

Abstract

BackgroundThe 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.MethodsWe performed whole-exome sequencing analysis of mediastinal GCT and acute myeloid leukemia (AML) samples obtained from one young Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them.ResultsSixteen 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.ConclusionsAll 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.

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications

“…Considering the entire cohort analyzed by Taylor et al, the most frequently altered gene was TP53, which affects 91% of MGCTs with secondary HMs [69]. This is consistent with the previous case reports of NGS analysis in which TP53 alterations were detected in all cases tested (Table 1) [72][73][74][75][76][77]. Interestingly, the frequency of TP53 is slightly greater than the one reported in all NS-MGCTs regardless of the HM onset (82% cases) [40].…”

“…For example, gain or isochromosome of 12p is an event not detectable in canonical AML [69], but it has been reported in 18 out of 38 HMs associated with MGCTs (approximately 47% of cases) (Table 2) [66,[68][69][70][71][72][73][74]76]. Conversely common alterations, including MLL rearrangements or mutations on genes such as FLT3, NPM1 and others, were not detected in AML coupled with MGCTs [67,69,72,77,78].…”

“…Evidence of a clonal relationship between HM and MGCT was discovered through the identification of molecular alterations shared between the two tumor types (i12p/12p gain, TP53, KRAS and PTEN mutations) (Table 1) [66,[68][69][70][71][72][73][74][75][76][77][78][79][80]. Moreover, the hematologic disease frequently carries alterations not typical of the specific type of HM and lacks the canonical aberrations detected in de novo diseases.…”

To Be or Not to Be a Germ Cell: The Extragonadal Germ Cell Tumor Paradigm

“…Genetic conditions such as Klinefelter syndrome (KS), Marfan syndrome or Down syndrome, as well as somatic mutations of genes involved in PGC proliferation have been shown to associate with EGCTs, which can appear either in childhood or in the post-puberal age [ 13 , 14 , 15 , 16 ].…”

STAT3‑PTTG11 abrogation inhibits proliferation and induces apoptosis in malignant glioma cells

“…Human pituitary tumor-transforming gene 1 (PTTG11) is a multifunctional proto-oncogene that is upregulated in various tumors, including glioma and hepatocellular carcinoma (9). The upregulation of PTTG11 is associated with tumor invasion, progression and angiogenesis, suggesting that PTTG1 may play a crucial role in tumorigenesis (10). PTTG1 has been identified as a key 'signature gene', with high levels of expression predicting metastasis in multiple tumor types, such as breast, prostate and ovarian cancer (11).…”