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Cancer Res. 2014 May 15;74(10):2742-9. doi: 10.1158/0008-5472.CAN-13-2470. Epub 2014 Mar 27.

Biallelic DICER1 mutations in sporadic pleuropulmonary blastoma.

Author information

1
Authors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, Japan.
2
Authors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, JapanAuthors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, Japan.
3
Authors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, JapanAuthors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, JapanAuthors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and
4
Authors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, JapanAuthors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, Japan jtakita-tky@umin.ac.jp sogawa-tky@umin.ac.jp.
5
Authors' Affiliations: Department of Pediatrics; Cancer Genomics Project, Graduate School of Medicine; Laboratory of DNA Information Analysis and Sequence Data Analysis, Human Genome Center, Institute of Medical Science; Department of Cell Therapy and Transplantation Medicine, The University of Tokyo, Tokyo; Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto; Division of Pediatric Hematology and Oncology, Ibaraki Children's Hospital, Mito, Ibaraki; Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Saitama; Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka; Gunma Children's Medical Center, Shibukawa, Gunma; Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Hyogo; and National Center for Child Health and Development, Tokyo, Japan jtakita-tky@umin.ac.jp sogawa-tky@umin.ac.jp.

Abstract

Pleuropulmonary blastoma (PPB) is a rare pediatric malignancy whose pathogens are poorly understood. Recent reports suggest that germline mutations in the microRNA-processing enzyme DICER1 may contribute to PPB development. To investigate the genetic basis of this cancer, we performed whole-exome sequencing or targeted deep sequencing of multiple cases of PPB. We found biallelic DICER1 mutations to be very common, more common than TP53 mutations also found in many tumors. Somatic ribonuclease III (RNase IIIb) domain mutations were identified in all evaluable cases, either in the presence or absence of nonsense/frameshift mutations. Most cases had mutated DICER1 alleles in the germline with or without an additional somatic mutation in the remaining allele, whereas other cases displayed somatic mutations exclusively where the RNase IIIb domain was invariably affected. Our results highlight the role of RNase IIIb domain mutations in DICER1 along with TP53 inactivation in PPB pathogenesis.

PMID:
24675358
DOI:
10.1158/0008-5472.CAN-13-2470
[Indexed for MEDLINE]
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