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

Kris Ann P. Schultz, Alexander T. Nelson, Paige H.R. Mallinger, Anne K. Harris, Junne Kamihara, Shari Baldinger, Kenneth S. Chen, Dinel Pond, Jessica N. Hatton, Anna G. Dybvik, Sarah G. Mitchell, Melissa R. Perrino, Tal Ben-Ami, Denis Kachanov, Yan Su, Chao Duan, Damon R. Olson, Dave Watson, Amanda L. Field, Laura A. HarneyAnn Garrity Carr, A. Lindsay Frazier, Dominik T. Schneider, David B. Wilson, Suzanne P. MacFarland, Peter J. Schoettler, Andrew J. Bauer, Louis P. Dehner, Dana Ashley Hill, Douglas R. Stewart, Yoav H. Messinger

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)5681-5692
Number of pages12
JournalClinical Cancer Research
Volume30
Issue number24
DOIs
StatePublished - Dec 15 2024

Fingerprint

Dive into the research topics of 'DICER1-Related Tumor Predisposition: Identification of At-risk Individuals and Recommended Surveillance Strategies'. Together they form a unique fingerprint.

Cite this