Extraskeletal chondroma of the toe in a child with DICER1 tumor predisposition syndrome: support for a dominant negative mechanism.

Autor: Pelletier D; Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.; Faculty of Medicine, Université de Montréal, Montreal, QC, Canada., Sabbaghian N; Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada., Chong AL; Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada.; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada., Priest JR; Minneapolis, USA., Elsheikh Ahmed Y; Sunnybrook Health Sciences Centre, Toronto, ON, Canada.; Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen, Bahrain.; King Hamad University Hospital, Al Sayh, Bahrain., Fox GP; Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen, Bahrain.; King Hamad University Hospital, Al Sayh, Bahrain., Fabian MR; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada., Foulkes WD; Department of Human Genetics, Medicine, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca.; Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada. william.foulkes@mcgill.ca.; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. william.foulkes@mcgill.ca.; Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, QC, Canada. william.foulkes@mcgill.ca.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2024 Jun; Vol. 484 (6), pp. 1023-1027. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1007/s00428-024-03759-y
Abstrakt: DICER1 tumor predisposition syndrome is a pleiotropic disorder that gives rise to various mainly pediatric-onset lesions. We report an extraskeletal chondroma (EC) of the great toe occurring in a child who, unusually, carries a germline "hotspot" missense DICER1 variant rather than the more usual loss-of-function (LOF) variant. No heterozygous LOF allele was identified in the EC. We demonstrate this variant impairs 5p cleavage of precursor-miRNA (pre-miRNA) and competes with wild-type (WT) DICER1 protein for pre-miRNA processing. These results suggest a mechanism through which a germline RNase IIIb variant could impair pre-miRNA processing without complete LOF of the WT DICER1 allele.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: