Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Clin Cancer Res. 2017 Jun 15;23(12):e62-e67. doi: 10.1158/1078-0432.CCR-17-0595.

Abstract

Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU)SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in SUFU mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive "rhabdoid" term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, each of which encodes a chromatin remodeling family member. SMARCA4 mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of SMARCB1 and SMARCA4 mutations. Clin Cancer Res; 23(12); e62-e67. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

Publication types

  • Review

MeSH terms

  • Basal Cell Nevus Syndrome / diagnosis
  • Basal Cell Nevus Syndrome / genetics*
  • Basal Cell Nevus Syndrome / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child, Preschool
  • Chromatin Assembly and Disassembly / genetics
  • DNA Helicases / genetics*
  • Germ-Line Mutation
  • Humans
  • Infant
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Nuclear Proteins / genetics*
  • Patched-1 Receptor / genetics
  • Repressor Proteins / genetics
  • Rhabdoid Tumor / diagnosis
  • Rhabdoid Tumor / genetics*
  • Rhabdoid Tumor / pathology
  • SMARCB1 Protein / genetics*
  • Transcription Factors / genetics*

Substances

  • Nuclear Proteins
  • PTCH1 protein, human
  • Patched-1 Receptor
  • Repressor Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • SUFU protein, human
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases

Supplementary concepts

  • Rhabdoid Tumor Predisposition Syndrome 1