Rhabdoid tumor predisposition syndrome

Pediatr Dev Pathol. 2015 Jan-Feb;18(1):49-58. doi: 10.2350/14-07-1531-MISC.1. Epub 2014 Dec 10.

Abstract

Rhabdoid tumors (RT), or malignant rhabdoid tumors, are among the most aggressive and lethal forms of human cancer. They can arise in any location in the body but are most commonly observed in the brain, where they are called atypical teratoid/rhabdoid tumors (AT/RT), and in the kidneys, where they are called rhabdoid tumors of the kidney. The vast majority of rhabdoid tumors present with a loss of function in the SMARCB1 gene, also known as INI1, BAF47, and hSNF5, a core member of the SWI/SNF chromatin-remodeling complex. Recently, mutations in a 2nd locus of the SWI/SNF complex, the SMARCA4 gene, also known as BRG1, were found in rhabdoid tumors with retention of SMARCB1 expression. Familial cases may occur in a condition known as rhabdoid tumor predisposition syndrome (RTPS). In RTPS, germline inactivation of 1 allele of a gene occurs. When the mutation occurs in the SMARCB1 gene, the syndrome is called RTPS1, and when the mutation occurs in the SMARCA4 gene it is called RTPS2. Children presenting with RTPS tend to develop tumors at a younger age, but the impact that germline mutation has on survival remains unclear. Adults who carry the mutation tend to develop multiple schwannomas. The diagnosis of RTPS should be considered in patients with RT, especially if they have multiple primary tumors, and/or in individuals with a family history of RT. Because germline mutations result in an increased risk of carriers developing RT, genetic counseling for families with this condition is recommended.

Keywords: AT/RT; SMARCA4; SMARCB1; malignant rhabdoid tumors; rhabdoid tumor predisposition syndrome; schwannomatosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Child
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone / genetics
  • DNA Helicases / genetics
  • DNA-Binding Proteins / genetics
  • Diagnosis, Differential
  • Family Health
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Male
  • Neurilemmoma / genetics
  • Neurofibromatoses / genetics
  • Nuclear Proteins / genetics
  • Rhabdoid Tumor / classification
  • Rhabdoid Tumor / diagnosis*
  • Rhabdoid Tumor / genetics*
  • SMARCB1 Protein
  • Skin Neoplasms / genetics
  • Transcription Factors / genetics

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases

Supplementary concepts

  • Schwannomatosis