+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes



Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes



Human Molecular Genetics 23(22): 6008-6021



Endometriosis is a complex and enigmatic disease that arises from the interplay among multiple genetic and environmental factors. The defining feature of endometriosis is the deposition and growth of endometrial tissues at sites outside of the uterine cavity. Studies to date have established that endometriosis is heritable but have not addressed the causal genetic variants for this disease. Here, we conducted whole-exome sequencing to comprehensively search for somatic mutations in both eutopic and ectopic endometrium from 16 endometriosis patients and five normal control patients using laser capture microdissection. We compared the mutational landscape of ectopic endometrium with the corresponding eutopic sample from endometriosis patients compared with endometrium from normal women and identified previously unreported mutated genes and pathway alternations. Statistical analysis of exome data identified that most genes were specifically mutated in both eutopic and ectopic endometrium cells. In particular, genes that are involved in biological adhesion, cell-cell junctions, and chromatin-remodeling complex(es) were identified, which partially supports the retrograde menstruation theory that proposes that endometrial cells are refluxed through the fallopian tubes during menstruation and implanted onto the peritoneum or pelvic organs. Conspicuously, when we compared exomic mutation data for paired eutopic and ectopic endometrium, we identified a mutational signature in both endometrial types for which no overlap in somatic single nucleotide variants were observed. These mutations occurred in a mutually exclusive manner, likely because of the discrepancy in endometriosis pathology and physiology, as eutopic endometrium rapidly regrows, and ectopic endometrial growth is inert. Our findings provide, to our knowledge, an unbiased view of the landscape of genetic alterations in endometriosis and vital information for indicating that genetic alterations in cytoskeletal and chromatin-remodeling proteins could be involved in the pathogenesis of endometriosis, thus implicating a novel therapeutic possibility for endometriosis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 056942293

Download citation: RISBibTeXText

PMID: 24969084

DOI: 10.1093/hmg/ddu330


Related references

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nature Genetics 44(5): 570-574, 2012

Whole-Exome Sequencing Reveals Frequent Mutations in Chromatin Remodeling Genes in Mammary and Extramammary Paget's Diseases. Journal of Investigative Dermatology 139(4): 789-795, 2019

Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nature Genetics 44(12): 1310-1315, 2012

Integrated Whole Exome Sequencing And Homozygosity Mapping Identifies Variants In Known And Novel Autism Genes Involved In Neuronal Migration And Adhesion Pathways. European Neuropsychopharmacology 29: S894-S895, 2019

Targeted genomic sequencing of pediatric Burkitt lymphoma identifies recurrent alterations in antiapoptotic and chromatin-remodeling genes. Blood 120(26): 5181-5184, 2013

Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling genes. Clinical Cancer Research 20(15): 4129-4140, 2015

Whole exome sequencing identifies hemizygous deletions in the UGT2B28 and USP17L2 genes in a three‑generation family with endometriosis. Molecular Medicine Reports 2019, 2019

RNA sequencing analysis identifies new human collagen genes involved in cardiac remodeling. Journal of the American College of Cardiology 65(12): 1265-1267, 2015

Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia. Plos One 9(10): E110740, 2015

Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function. Journal of Alzheimer's Disease and Parkinsonism 7(4), 2017

Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nature Genetics 45(2): 186-190, 2012

Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12. Plos Genetics 12(2): E1005850, 2016

Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2 , TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma. Haematologica 102(10): 1758-1766, 2017

Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome. American Journal of Human Genetics 87(3): 418-423, 2010

A Survey of Somatic Mutations in 41 Genes in a Cohort of T-Cell Lymphomas Identifies Frequent Mutations in Genes Involved in Epigenetic Modification. Applied Immunohistochemistry and Molecular Morphology 2018, 2018