The prevalence of germline DICER1 pathogenic variation in cancer populations

Jung Kim, Kris Ann P. Schultz, Dana Ashley Hill, Douglas R. Stewart

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Background: The DICER1 syndrome is an autosomal dominant tumor-predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense variation in “hotspot” codons in the RNaseIIIb domain (E1705, D1709, G1809, D1810, E1813) is observed in DICER1-associated tumors. Previously, we found the prevalence of germline pathogenic DICER1 variation in the general population is 1:10,600. In this study, we investigated the prevalence of pathogenic DICER1 germline variation in The Cancer Genome Atlas (TCGA; 32 adult cancer types; 9,173 exomes) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET; two pediatric cancer types; 175 exomes) cohorts. Methods: All datasets were annotated and binned into four categories: pathogenic, likely pathogenic, variant of unknown significance, or likely benign. Results: The prevalence of DICER1 pathogenic variants was 1:4,600 in TCGA. A single participant with a uterine corpus endometrial carcinoma harbored two pathogenic germline DICER1 (hotspot and splice-donor) variants, and a single participant with a rectal adenocarcinoma harbored a germline DICER1 stop-gained variant. In the smaller TARGET dataset, we observed no pathogenic germline variants. Conclusion: This is the largest comprehensive analysis of DICER1 pathogenic variation in adult and pediatric cancer populations using publicly available data. The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.

Original languageEnglish
Article numbere555
JournalMolecular Genetics and Genomic Medicine
Volume7
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • DICER1
  • DICER1 syndrome
  • TARGET
  • TCGA
  • cancer population
  • prevalence estimate

Fingerprint

Dive into the research topics of 'The prevalence of germline DICER1 pathogenic variation in cancer populations'. Together they form a unique fingerprint.

Cite this