The genomic landscape of pediatric renal cell carcinomas
Pengbo Beck,
Barbara Selle,
Lukas Madenach,
David T.W. Jones,
Christian Vokuhl,
Apurva Gopisetty,
Arash Nabbi,
Ines B. Brecht,
Martin Ebinger,
Jenny Wegert,
Norbert Graf,
Manfred Gessler,
Stefan M. Pfister,
Natalie Jäger
Affiliations
Pengbo Beck
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
Barbara Selle
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany
Lukas Madenach
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
David T.W. Jones
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Pediatric Glioma Research Group, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Christian Vokuhl
Section of Pediatric Pathology, Department of Pathology, University Hospital Bonn, Bonn, Germany
Apurva Gopisetty
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany
Arash Nabbi
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
Ines B. Brecht
Department of Pediatric Oncology and Hematology, University Children's Hospital Tübingen, Tübingen, Germany
Martin Ebinger
Department of Pediatric Oncology and Hematology, University Children's Hospital Tübingen, Tübingen, Germany
Jenny Wegert
Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University & Comprehensive Cancer Center Mainfranken, Würzburg, Germany
Norbert Graf
Department of Pediatric Oncology and Hematology, Saarland University, Homburg, Germany
Manfred Gessler
Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Würzburg University & Comprehensive Cancer Center Mainfranken, Würzburg, Germany
Stefan M. Pfister
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
Natalie Jäger
Hopp Children’s Cancer Center Heidelberg (KiTZ) & Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Corresponding author
Summary: Pediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes but also in clinical characteristics and outcome. However, the underlying biology is still largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various histologic subtypes, including 10 MiT family translocation (MiT) and 10 papillary RCCs. In this cohort of pediatric RCC, we find only limited genomic overlap with adult RCC, even within the same histologic subtype. Recurrent somatic mutations in genes not previously reported in RCC were detected, such as in CCDC168, PLEKHA1, VWF, and MAP3K9. Our papillary pediatric RCCs, which represent the largest cohort to date with comprehensive molecular profiling in this age group, appeared as a distinct genomic subtype differing in terms of gene mutations and gene expression patterns not only from MiT-RCC but also from their adult counterparts.
