Intronic Germline DICER1 Variants in Patients With Sertoli-Leydig Cell Tumor.

Autor:	Fraire CR; Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX., Mallinger PR; International Pleuropulmonary Blastoma (PPB)/DICER1 Registry, Children's Minnesota, Minneapolis, MN.; International Ovarian and Testicular Stromal Tumor (OTST) Registry, Children's Minnesota, Minneapolis, MN.; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN., Hatton JN; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD., Kim J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD., Dickens DS; Department of Pediatrics, University of Iowa, Iowa City, IA., Argenta PA; Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN., Milanovich S; Pediatric Hematology and Oncology, Sanford Roger Maris Cancer Center, Fargo, ND., Hartshorne T; Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX., Carey DJ; Department of Genomic Health, Geisinger Clinic, Danville, PA., Haley JS; Department of Genomic Health, Geisinger Clinic, Danville, PA., Urban G; Department of Genomic Health, Geisinger Clinic, Danville, PA., Lee J; Lyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX., Hill DA; Department of Pathology and Immunology, Washington University, St Louis, MO., Stewart DR; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD., Schultz KAP; International Pleuropulmonary Blastoma (PPB)/DICER1 Registry, Children's Minnesota, Minneapolis, MN.; International Ovarian and Testicular Stromal Tumor (OTST) Registry, Children's Minnesota, Minneapolis, MN.; Cancer and Blood Disorders, Children's Minnesota, Minneapolis, MN., Chen KS; Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX.; Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2023 Sep; Vol. 7, pp. e2300189.
DOI:	10.1200/PO.23.00189
Abstrakt:	Germline pathogenic loss-of-function (pLOF) variants in DICER1 are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and Sertoli-Leydig cell tumor (SLCT). The most common DICER1 pLOF variants include small insertions or deletions leading to frameshifts, and base substitutions leading to nonsense codons or altered splice sites. Larger deletions and pathogenic missense variants occur less frequently. Identifying these variants can trigger surveillance algorithms with potential for early detection of DICER1 -related cancers and cascade testing of family members. However, some patients with DICER1 -associated tumors have no pLOF variants detected by germline or tumor testing. Here, we present two patients with SLCT whose tumor sequencing showed only a somatic missense DICER1 RNase IIIb variant. Conventional exon-directed germline sequencing revealed no pLOF variants. Using a custom capture panel, we discovered novel intronic variants, ENST00000343455.7: c.1752+213A>G and c.1509+16A>G, that appear to interfere with normal splicing. We suggest that when no DICER1 pLOF variants or large deletions are discovered in exonic regions despite strong clinical suspicion, intron sequencing and splicing analysis should be performed.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu