Characterization of Uterine Leiomyomas by Whole-Genome Sequencing

• Published in: The New England journal of medicine Vol. 369; no. 1; pp. 43 - 53
• Main Authors: Mehine, Miika, Kaasinen, Eevi, Mäkinen, Netta, Katainen, Riku, Kämpjärvi, Kati, Pitkänen, Esa, Heinonen, Hanna-Riikka, Bützow, Ralf, Kilpivaara, Outi, Kuosmanen, Anna, Ristolainen, Heikki, Gentile, Massimiliano, Sjöberg, Jari, Vahteristo, Pia, Aaltonen, Lauri A
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 04.07.2013
• Subjects: Benign; Biological and medical sciences; Cancer; Chromosome Aberrations; Chromosome Breakage; Chromosome Deletion; Chromosome rearrangements; Chromosome translocations; Chromosomes; Collagen Type IV - genetics; Deoxyribonucleic acid; DNA; Female; Female genital diseases; Fibroids; Fumarate Hydratase - deficiency; Fumarate Hydratase - genetics; Gene expression; Gene Expression Profiling; Gene Rearrangement; General aspects; Genes; Genome-Wide Association Study; Genomes; Genomics; Gynecology. Andrology. Obstetrics; Humans; Kinases; Leiomyoma - genetics; Mediator Complex - genetics; Medical sciences; Metabolism; Molecular modelling; Mutation; Myometrium; Myometrium - chemistry; Nodules; p53 Protein; Patients; Tumorigenesis; Tumors; Up-Regulation; Uterine Neoplasms - genetics; Uterus; Finland; Characterization; Medicine; Nucleotide sequence; Uterine diseases; Uterine leiomyoma; Benign neoplasm; Genome; Sequencing; Female genital diseases
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1302736

Some leiomyomas have chromosomal rearrangements implicating chromothripsis, a process involving the formation of complex chromosomal rearrangements. In three instances, tumors obtained from the same woman were documented to be clonally related. Uterine leiomyomas are benign smooth-muscle tumors with an estimated prevalence of 77% among women of reproductive age in the United States 1 and can cause a range of health problems. 2 According to a nationwide analysis of 518,828 hysterectomies performed in 2005 in the United States, 282,291 of the patients who underwent the procedure (54%) had leiomyomas. 3 Hormonal factors, family history, African ancestry, and obesity increase the risk of leiomyomas. 4 Presentation with multiple tumors is typical (an estimated average is six to seven 1 ). Whether leiomyosarcomas develop from leiomyomas or arise independently is not known. Uterine leiomyosarcoma is very rare, 5 and it . . .