title: Renal cell carcinoma harboring somatic TSC2 mutations in a child with methylmalonic acidemia.
abstract: Pediatric renal cell carcinoma (RCC) is a rare cancer that can be associated with inherited diseases including tuberous sclerosis complex (TSC) caused by germline mutations in TSC1 or TSC2. Somatic mutations in TSC1 and TSC2 have also been reported in adult RCC, which predict response to mTOR inhibitors. Here, we present the first case of RCC in a child with methylmalonic acidemia (MMA). Clinical whole exome sequencing of blood and tumor samples confirmed the diagnosis of MMA and revealed two somatic inactivating mutations in TSC2, suggesting the potential consideration of an mTOR inhibitor in the event of tumor recurrence.
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Samara L
authors.initials: SL
authors.lastname: Potter
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Venkatramani
authors.affiliation: Department of Pediatric, Division of Nephrology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
authors.forename: Scott
authors.initials: S
authors.lastname: Wenderfer
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Brett H
authors.initials: BH
authors.lastname: Graham
authors.affiliation: Department of Surgery, Texas Children's Hospital, Houston, Texas.|Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.|The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Sanjeev A
authors.initials: SA
authors.lastname: Vasudevan
authors.affiliation: Department of Radiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sher
authors.affiliation: Department of Pathology, Texas Children's Hospital, Houston, Texas.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.|The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.|Department of Pathology, Texas Children's Hospital, Houston, Texas.|Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.
authors.forename: Angshumoy
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
authors.affiliation: Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.|The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000235:genetics; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D000068338:Everolimus / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: TSC2; methylmalonic acidemia; renal cell carcinoma