Renal cell carcinoma harboring somatic TSC2 mutations in a child with methylmalonic acidemia

Pediatr Blood Cancer. 2017 May;64(5):10.1002/pbc.26286. doi: 10.1002/pbc.26286. Epub 2016 Oct 17.

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.

Keywords: TSC2; methylmalonic acidemia; renal cell carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / complications*
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / complications
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics*
  • Child
  • Everolimus / therapeutic use
  • Female
  • Humans
  • Kidney Neoplasms / complications
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics*
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antineoplastic Agents
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • temsirolimus
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus

Supplementary concepts

  • Methylmalonic acidemia