AB165. Whole-exome sequencing characterizes the landscape of somatic mutations and copy number variations in testicular germ cell tumor

Abstract Background Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. Methods The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes corresponding to copy number alterations (CNA) deletion and duplication region, functional annotation of was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region. Results In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YST). Moreover, POU5F1 was the most significant mutated gene with mutation frequency > 10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region) was found in 2 YST and nuclear staining in 2 dysgerminomas (DG) tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I-like receptor, Toll-like receptor, NF-kappa B and Jak–STAT. KRT4, RPL14, PCSK6, PABPC3 and SARM1 mutations were detected in both peripheral blood and tumor samples. Conclusions Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

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

BMC Cancer ◽

10.1186/s12885-019-6497-0 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Keiichi Akizuki ◽

Masaaki Sekine ◽

Yasunori Kogure ◽

Takuro Kameda ◽

Kotaro Shide ◽

...

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Germ Cell Tumor ◽

Somatic Mutations ◽

Cell Tumor ◽

Sequencing Analysis ◽

Male Adult ◽

Clonal Relationship ◽

Whole Exome

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 Japanese male adult patient with concurrent both tumors, and investigated the possible clonal relationship between them. Results Sixteen 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.

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

10.21203/rs.2.10010/v1 ◽

2019 ◽

Author(s):

Keiichi Akizuki ◽

Masaaki Sekine ◽

Yasunori Kogure ◽

Takuro Kameda ◽

Kotaro Shide ◽

...

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Germ Cell Tumor ◽

Somatic Mutations ◽

Cell Tumor ◽

Sequencing Analysis ◽

Male Adult ◽

Clonal Relationship ◽

Whole Exome

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.

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

10.21203/rs.2.10010/v2 ◽

2019 ◽

Author(s):

Keiichi Akizuki ◽

Masaaki Sekine ◽

Yasunori Kogure ◽

Takuro Kameda ◽

Kotaro Shide ◽

...

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Germ Cell Tumor ◽

Somatic Mutations ◽

Cell Tumor ◽

Sequencing Analysis ◽

Male Adult ◽

Clonal Relationship ◽

Whole Exome

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.

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

10.21203/rs.2.10010/v3 ◽

2019 ◽

Author(s):

Keiichi Akizuki ◽

Masaaki Sekine ◽

Yasunori Kogure ◽

Takuro Kameda ◽

Kotaro Shide ◽

...

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Germ Cell Tumor ◽

Somatic Mutations ◽

Cell Tumor ◽

Sequencing Analysis ◽

Male Adult ◽

Clonal Relationship ◽

Whole Exome

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 Japanese 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.

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MPC-08 CLINICOPATHOLOGICAL ANALYSIS OF 12P GAIN IN INTRACRANIAL GERM CELL TUMORS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz039.105 ◽

2019 ◽

Vol 1 (Supplement_2) ◽

pp. ii23-ii23

Author(s):

Kaishi Satomi ◽

Hirokazu Takami ◽

Shintaro Fukushima ◽

Yoichi Nakazato ◽

Shota Tanaka ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumor ◽

Copy Number ◽

Mature Teratoma ◽

Methylation Status ◽

Germ Cell Tumors ◽

Copy Number Variations ◽

Cell Tumor ◽

Testicular Germ Cell ◽

Intracranial Germ Cell Tumor

Abstract BACKGROUND Gain of short arm of chromosome 12 (12p) is commonly observed in testicular germ cell tumors (tGCTs). 12p gain is also frequently seen in intracranial GCTs (iGCTs). However, little is known about the clinical significance of 12p gain in iGCTs. MATERIALS AND METHODS We have collected over 200 fresh frozen tissue samples of iGCTs through the Intracranial Germ Cell Tumor Genome Analysis Consortium in Japan. Firstly, we analyzed DNA methylation status in 83 iGCTs, 3 seminomas and 6 normal control samples using Infinium Human Methylation 450K BeadChip array (Illumina, CA). Idat files were processed using R (Version 3.5.3) and minfi package (1.30.0) to generate copy number variations. Compared with average genome-wide copy number level, 12p gain was determined. Then, 58 iGCTs with clinicopathological information were analyzed for progression-free survival (PFS) and overall survival (OS). Those tumors that consist of only either germinoma and/or mature teratoma components were classified as Favorable Histology (FH) and all the others that contains malignant histological components were classified as Unfavorable Histology (UFH). RESULT 12p gain was observed in 100% (3/3) of seminoma, 13.6% (3/22) of germinoma, 16.7% (1/6) of mature teratoma, 25% (1/4) of immature teratoma, 55% (11/20) of mixed germ cell tumor, 100% (4/4) of yolk sac tumor, 100% (1/1) of embryonal carcinoma, and 100% (1/1) of choriocarcinoma. In total, 44.6% (37/83) of iGCT showed 12p gain. Regarding histological classification, the 12p gain rate in UFH (72%, 18/25) was significantly higher than that in FH (12.1%, 4/33, P<0.01). Both PFS and OS were significantly worse in iGCTs with 12p gain (PFS: P=0.027, OS: P=0.0012). DISCUSSION 12p gain can be a molecular marker to predict prognosis and histological malignancy in iGCTs.

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