DICER1-Related Tumor Predisposition: Identification of At-risk Individuals and Recommended Surveillance Strategies

Clin Cancer Res. 2024 Dec 16;30(24):5681-5692. doi: 10.1158/1078-0432.CCR-24-1532.

Abstract

Purpose: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the goals of the Registry is to continue to refine these guidelines as additional data become available.

Experimental design: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the NCI Natural History of DICER1 Syndrome study.

Results: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli-Leydig cell tumor at a median age of 14 years (range: 11 months-66 years); 13% were diagnosed before 8 years of age, the current age of onset of pelvic surveillance. Additionally, 4% of Sertoli-Leydig cell tumors were diagnosed before 4 years of age.

Conclusions: Ongoing data collection highlights the role of lung surveillance in the early detection of PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before 8 years of age, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • DEAD-box RNA Helicases* / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Pulmonary Blastoma* / diagnosis
  • Pulmonary Blastoma* / genetics
  • Pulmonary Blastoma* / pathology
  • Registries*
  • Ribonuclease III* / genetics
  • Sertoli-Leydig Cell Tumor / diagnosis
  • Sertoli-Leydig Cell Tumor / genetics
  • Sertoli-Leydig Cell Tumor / pathology
  • Young Adult

Substances

  • Ribonuclease III
  • DICER1 protein, human
  • DEAD-box RNA Helicases

Supplementary concepts

  • Pleuropulmonary blastoma