Format

Send to

Choose Destination
Mol Genet Genomic Med. 2019 Jan 22:e555. doi: 10.1002/mgg3.555. [Epub ahead of print]

The prevalence of germline DICER1 pathogenic variation in cancer populations.

Author information

1
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland.
2
Cancer and Blood Disorders, Children's Minnesota, Minneapolis, Minnesota.
3
International Pleuropulmonary Blastoma/DICER1 Registry, Minneapolis, Minnesota.
4
International Ovarian and Testicular Stromal Tumor Registry, Minneapolis, Minnesota.
5
Division of Pathology and Center for Cancer and Immunology Research, Children's National Health System, Washington, District of Columbia.

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.

KEYWORDS:

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

PMID:
30672147
DOI:
10.1002/mgg3.555
Free full text

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center