Recurrent Somatic DICER1 Mutations in Nonepithelial Ovarian Cancers

• Published in: The New England journal of medicine Vol. 366; no. 3; pp. 234 - 242
• Main Authors: Heravi-Moussavi, Alireza, Anglesio, Michael S, Cheng, S.-W. Grace, Senz, Janine, Yang, Winnie, Prentice, Leah, Fejes, Anthony P, Chow, Christine, Tone, Alicia, Kalloger, Steve E, Hamel, Nancy, Roth, Andrew, Ha, Gavin, Wan, Adrian N.C, Maines-Bandiera, Sarah, Salamanca, Clara, Pasini, Barbara, Clarke, Blaise A, Lee, Cheng-Han, Lee, Anna F, Zhao, Chengquan, Young, Robert H, Aparicio, Samuel A, Sorensen, Poul H.B, Woo, Michelle M.M, Boyd, Niki, Jones, Steven J.M, Hirst, Martin, Marra, Marco A, Gilks, Blake, Shah, Sohrab P, Foulkes, William D, Morin, Gregg B, Huntsman, David G
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 19.01.2012
• Subjects: Biological and medical sciences; Cancer; Carcinosarcoma - genetics; Codons; DEAD-box RNA Helicases - genetics; Deoxyribonucleic acid; DNA; Dysplasia; Endometrial cancer; Endometrium; Enzymatic activity; Female; Female genital diseases; Gene Expression; Gene Expression Profiling; General aspects; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; MicroRNAs - metabolism; miRNA; Missense mutation; Mutation; Mutation, Missense; Neoplasms, Germ Cell and Embryonal - genetics; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - genetics; Rhabdomyosarcoma - genetics; Ribonuclease III; Ribonuclease III - genetics; Sequence Analysis, DNA; Sertoli-Leydig Cell Tumor - genetics; Tumors; Uterine cancer; British Columbia Canada; Canada; Somatic mutation; Medicine; Ovarian diseases; Relapse; Ovary cancer; Recurrent; Malignant tumor; Cancer; Female genital diseases
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1102903

Primitive cancers have so-called hot-spot mutations in DICER1 that alter the function of DICER1, an enzyme that processes microRNA. Some of these cancers harbor a loss-of-function mutation in the other DICER1 allele, suggesting a new mutational mechanism of oncogenesis. Sex cord–stromal tumors and germ-cell tumors account for less than 10% of ovarian cancers. 1 Unlike epithelial ovarian cancers, both sex cord–stromal tumors and germ-cell tumors can also occur in the testicle; testicular germ-cell tumors are the most common cancer in boys and men of European descent between the ages of 15 and 34 years. 2 , 3 Other than a pathognomonic somatic mutation in FOXL2 in adult granulosa-cell tumors, 4 – 6 little is known about the pathogenesis of ovarian sex cord–stromal tumors and germ-cell tumors. Recently, germline mutations in the microRNA processing gene DICER1 have been reported in probands with pleuropulmonary blastoma or . . .