Abstract
Objective: To test the hypothesis that endometriosis may originate from genomic alterations
in the endometrium by genomic analysis of endometrial tissues in patients with endometriosis
and compare them with those from normal controls. Methods: Endometrial tissue samples were taken from five women with endometriosis. For controls,
we used endometrial tissue samples from four women who underwent elective abortions
and one sample from placenta. Using array-based comparative genomic hybridization
(CGH), we determined the normal range of variation in CGH signals using normal controls.
CGH results were further confirmed by real-time quantitative PCR and loss of heterozygosity
analysis. Results: We identified several regions of genomic alterations in all five patients. Some
of these regions were the same regions identified previously in endometriotic lesions.
For select markers, the genomic alterations were confirmed by real-time PCR and LOH
analyses. Conclusions: There is evidence that the endometrium in women with endometriosis has genomic alterations.
This is consistent with numerous reports that the endometrium of women with endometriosis
differ from those of women without. Our finding suggests that genomic alterations
in the endometrium may be a proximate cause for endometriosis.
Keywords
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References
- Endometriosis.N. Engl. J. Med. 1993; 328: 1759-1769
- Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity.Am. J. Obstet. Gynecol. 1927; 14: 422-469
- The histogenesis of endometriosis: a review of facts and fancies.Obstet. Gynecol. Surv. 1968; 23: 1-35
- Current concepts in the pathogenesis of endometriosis.Clin Obstet. Gynecol. 1999; 42: 566-585
- The relation of endometriosis to menstrual characteristics, smoking, and exercise.JAMA. 1986; 255: 1904-1908
- Menstrual cycle characteristics and the risk of endometriosis.Epidemiology. 1993; 4: 135-142
- Menstrual characteristics in women with and without endometriosis.Obstet. Gynecol. 1997; 90: 264-268
- Menstrual characteristics associated with endometriosis.Br. J. Obstet. Gynaecol. 1997; 104: 948-950
- Experimental endometriosis.Am. J. Obstet. Gynecol. 1950; 60: 1147-1173
- Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis).Am. J. Obstet. Gynecol. 1995; 173: 125-134
- Endometriosis and mullerian anomalies.Obstet. Gynecol. 1987; 69: 412-415
- Endometriosis in association with uterine anomaly.Am. J. Obstet. Gynecol. 1984; 154: 39-43
- Retrograde menstruation in healthy women and in patients with endometriosis.Obstet. Gynecol. 1984; 64: 151-154
- Endometriosis: its association with retrograde menstruation, dysmenorrhoea and tubal pathology.Br. J. Obstet. Gynaecol. 1986; 93: 859-862
Nagel T, Kopher R, Tagatz G. Tubal refulx of endomerial tissue during hysteroscopy. In: Siegler AM, Lindemann HJ, editors. Hysteroscopy: principles and practice. Philadelphia, PA: JB Lippincott; 1984.
- Abdominal dissemination of malignant cells wit hysteroscopy.Gynecol. Oncol. 1996; 63: 143-144
- The viability of the cast-off menstrual endometrium.Am. J. Obstet. Gynecol. 1951; 61: 440
- Experimental endometriosis in the human.Am. J. Obstet. Gynecol. 1958; 76: 783-789
- Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors.Science. 1992; 258: 818-821
- Minimal sizes of deletions detected by comparative genomic hybridization.Genes Chromosomes Cancer. 1998; 21: 172-175
- Deletions below 10 megabasepairs are detected in comparative genomic hybridization by standard reference intervals.Genes Chromosomes Cancer. 1999; 25: 410-413
- Comparative genomic hybridization: uses and limitations.Semin Hematol. 2000; 37: 348-357
- High-throughput analysis of subtelomeric chromosome rearrangements by use of array-based comparative genomic hybridization.Am. J. Hum. Genet. 2002; 70: 1269-1276
- Automated screening for genomic imbalances using matrix-based comparative genomic hybridization.Lab. Invest. 2002; 82: 47-60
- Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances.Genes Chromosomes Cancer. 1997; 20: 399-407
- High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays.Nat Genet. 1998; 20: 207-211
- Genome-wide analysis of DNA copy-number changes using cDNA microarrays.Nat. Genet. 1999; 23: 41-46
- Assembly of microarrays for genome-wide measurement of DNA copy number.Nat Genet. 2001; 29: 263-264
- Quantitative quality control in microarray image processing and data acquisition.Nucleic Acids Res. 2001; 29: E75-E85
- Measurement of DNA copy number at microsatellite loci using quantitative PCR analysis.Cancer Res. 2000; 60: 5405-5409
- Detection of 1pN and 19q loss in oligodendroglioma by quantitative microsatellite analysis, a real-time quantitative polymerase chain reaction assay.Am. J. Pathol. 2001; 158: 1253-1262
- Substrate nucleotide-determined non-templated addition of adenine by Taq DNA polymerase: implications for PCR-based genotyping and cloning.Biotechniques. 1996; 21: 700-709
- Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation.Nucleic Acids Res. 2002; 30: E15
- Statistical methods for detecting genomic alterations through array-based comparative genomic hybridization (CGH).Front Biosci. 2004; 9: 540-549
- Evidence for monoclonal expansion of epithelial cells in ovarian endometrial cysts.Am. J. Pathol. 1997; 150: 1173-1178
- Detection of DNA copy number changes in human endometriosis by comparative genomic hybridization.Hum Genet. 1999; 105: 444-451
- Polyploidy in the human endometrium with the Arias-Stella reaction.Arch. Pathol. 1968; 85: 475-480
Anderson MC, Robboy SJ, Russell P, Morse A. Cervix—benign and non-neoplastic conditions. In: Robboy SJ, Anderson MC, Russell P, editors. Pathology of the female reproductive tract. New York: Churchill Livingstone; 2002. p. 105–35.
- Genetic characterization of lung metastases in renal cell carcinoma.Oncol. Rep. 2003; 10: 1035-1038
- Grade II astrocytomas are subgrouped by chromosome aberrations.Cancer Genet Cytogenet. 2003; 142: 1-7
- DNA microarrays for comparative genomic hybridization based on DOP-PCR amplification of BAC and PAC clones.Genes Chromosomes Cancer. 2003; 36 (Erratum in: Genes Chromosomes Cancer 2003;37:223): 361-374
- Monoclonal origin of endometriotic cysts.Int. J. Gynecol. Cancer. 1995; 5: 61-63
- Molecular analysis of clonality in ovarian endometrial cysts.Gynecol. Obstet. Invest. 1999; 47: 41-45
- Resolution of clonal origins for endometriotic lesions using laser capture microdissection and human androgen receptor (HUMARA) assay.Fertil. Steril. 2003; 79: 710-717
- Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci.Cancer Res. 1996; 56: 3534-3539
- Somatic DNA alterations in endometriosis: high frequency of chromosome 17 and p53 loss in late-stage endometriosis.J. Reprod. Immunol. 2002; 55: 49-64
- Detection of chromosomal aneuploidy in endometriosis by multi-color fluorescence in situ hybridization (FISH).Hum Genet. 1997; 100: 401-406
- Increased heterogeneity of chromosome 17 aneuploidy in endometriosis.Am. J. Obstet. Gynecol. 1999; 180: 792-797
- Microsatellite DNA assays reveal an allelic imbalance in p16(Ink4), GALT, p53, and APOA2 loci in patients with endometriosis.Fertil. Steril. 2001; 75: 160-165
- Regulated commitment of TNF receptor signaling: a molecular switch for death or activation.Immunity. 1999; 11: 783-793
- Transcriptional inactivation of TP73 expression in oligodendroglial tumors.Int. J. Cancer. 2002; 98: 370-375
- Endometriosis in 1,000 consecutive celiotomies: incidence and management.Am. J. Obstet. Gynecol. 1997; 129: 245-250
- Unsuspected endometriosis documented by scanning electron microscopy in visually normal peritoneum.Fertil. Steril. 1986; 46: 522-524
- Prevalence of endometriosis in asymptomatic women.J. Reprod. Med. 1991; 36: 513-515
- Radiation- and chemical-induced structural chromosome aberrations in human spermatozoa.Mutat. Res. 2002; 504: 183-191
- The human cornea has a high incidence of acquired chromosome abnormalities.Hum Genet. 1997; 101: 26-29
- Radioactive estradiol accumulation in endometriosis of the rhesus monkey.Am. J. Obstet. Gynecol. 1971; 109: 124-130
- Disseminated endometriosis in a rhesus monkey (Macaca mulatta). Histogenesis and possible relationship to irradiation exposure 1, 2.J. Med. Assoc. Ga. 1971; 60: 11-13
- Endometriosis in four irradiated rhesus monkeys.Vet. Pathol. 1972; 9: 249-262
- Endometriosis in rhesus monkeys.Lab. Anim. 1982; 16: 281-284
- Proton irradiation and endometriosis.Aviat. Space Environ. Med. 1983; 54: 718-724
- Radiation-induced endometriosis in Macaca mulatta.Radiat. Res. 1991; 126: 141-146
- Long-term mortality and cancer risk in irradiated rhesus monkeys.Radiat. Res. 1991; 126: 132-140
- Occupational exposures and risk of female infertility.J. Occup. Environ. Med. 1997; 39: 138-147
- Theories of endometriosis.Eur. J. Obstet. Gynecol. Reprod. Biol. 2001; 96: 21-34
- Is endometriosis an endometrial disease?.Eur. J. Obstet. Gynecol. Reprod. Biol. 2000; 91: 113-125
- Cell proliferation is increased in the endometrium of women with endometriosis.Fertil. Steril. 1995; 64: 340-346
- Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis.Hum Reprod. 2001; 16: 1802-1808
- Aberrant integrin expression in the endometrium of women with endometriosis.J. Clin Endocrinol. Metab. 1994; 79: 643-649
- Integrin adhesion molecules in the endometrial glandular epithelium in patients with endometriosis or adenomyosis.J. Obstet. Gynaecol. Res. 1997; 23: 485-491
- HOX gene expression is altered in the endometrium of women with endometriosis.Hum Reprod. 1999; 14: 1328-1331
- Recurrence of chocolate cysts after laparoscopic ablation.J. Am. Assoc. Gynecol. Laparosc. 2002; 9: 315-320
- Endometriosis: absence of recurrence in patients after endometrial ablation.Hum Reprod. 2001; 16: 2676-2679
Albertson DG, Rauen KA, Cotter PD, Segraves R, Tokuyasu TA, Harris J, et al. High-resolution array CGH: a validation study for the detection of submicroscopic deletions in DiGeorge and velo-cardio-facial syndromes. Am J Hum Genet 73(Suppl):A208 [abstract].
Odeh RE, Owen DB, Tables for normal tolerance limits, sampling plans, and screening. New York: Marcel Dekker Inc., 1980. p. 128.
Article info
Publication history
Accepted:
February 3,
2004
Received in revised form:
December 9,
2003
Received:
October 20,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
