RT Journal Article
SR Electronic
T1 Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 011304
DO 10.1101/011304
A1 Leanne de Kock
A1 Harriet Druker
A1 Evan Weber
A1 Nancy Hamel
A1 Jeffery Traubici
A1 David Malkin
A1 Jocelyne Arseneau
A1 Dorothée Bouron-Dal Soglio
A1 John R. Priest
A1 William D. Foulkes
YR 2014
UL http://biorxiv.org/content/early/2014/11/10/011304.abstract
AB Embryonal rhabdomyosarcoma (ERMS), a malignant soft tissue sarcoma, is one of the most common paediatric cancers. Certain ERMS tumours are associated with the DICER1 syndrome, a distinctive tumour predisposition syndrome caused by germ-line mutations in the microRNA-maturation pathway gene, DICER1. In addition to germ-line DICER1 mutations, highly characteristic somatic mutations have been identified in several DICER1-associated tumour types. These so-called “hotspot” mutations affect highly conserved amino acid residues central to the catalytic activity of the DICER1 ribonuclease IIIb domain.Primary ovarian ERMS (oERMS) is extremely rare. We present a case of a 6-year-old girl with an oERMS found to harbour two mutations in DICER1. In addition to the oERMS, the girl also exhibited other DICER1 phenotypes, including cystic nephroma (CN) and multinodular goitre. Somatic investigations of the CN revealed the presence of a hotspot DICER1 mutation different from that in the oERMS. Of particular interest is the CN presented at the age of 12 years, which is much older than previously reported age range of susceptibility (birth to four years of age).This report documents both germ-line and highly characteristic somatic DICER1 mutations in a case of oERMS, adding to the expanding spectrum of rare childhood tumours in the DICER1 syndrome.