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Multiomic analysis of uterine leiomyomas in self-described Black and White women: molecular insights into health disparities.
Bateman, Nicholas W; Abulez, Tamara; Tarney, Christopher M; Bariani, Maria V; Driscoll, Jordan A; Soltis, Anthony R; Zhou, Ming; Hood, Brian L; Litzi, Tracy; Conrads, Kelly A; Jackson, Amanda; Oliver, Julie; Ganakammal, Satishkumar Ranganathan; Schneider, Frank; Dalgard, Clifton L; Wilkerson, Matthew D; Smith, Barbara; Borda, Victor; O'Connor, Timothy; Segars, James; Shobeiri, S Abbas; Phippen, Neil T; Darcy, Kathleen M; Al-Hendy, Ayman; Conrads, Thomas P; Maxwell, George Larry.
Afiliação
  • Bateman NW; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of
  • Abulez T; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD.
  • Tarney CM; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of
  • Bariani MV; The University of Chicago College of Medicine, Chicago, IL.
  • Driscoll JA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD.
  • Soltis AR; The University of Chicago College of Medicine, Chicago, IL.
  • Zhou M; The American Genome Center, Center for Military Precision Health, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD.
  • Hood BL; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD.
  • Litzi T; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD.
  • Conrads KA; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD.
  • Jackson A; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD.
  • Oliver J; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD.
  • Ganakammal SR; Women's Health Integrated Research Center, Women's Service Line, Inova Health System, Falls Church, VA.
  • Schneider F; Emory University School of Medicine, Atlanta, GA.
  • Dalgard CL; The American Genome Center, Center for Military Precision Health, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD.
  • Wilkerson MD; The American Genome Center, Center for Military Precision Health, Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD.
  • Smith B; Johns Hopkins University Medical Center, Baltimore, MD.
  • Borda V; Program in Personalize and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD.
  • O'Connor T; Program in Personalize and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD.
  • Segars J; Johns Hopkins University Medical Center, Baltimore, MD.
  • Shobeiri SA; Women's Health Integrated Research Center, Women's Service Line, Inova Health System, Falls Church, VA.
  • Phippen NT; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of
  • Darcy KM; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of
  • Al-Hendy A; The University of Chicago College of Medicine, Chicago, IL.
  • Conrads TP; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of
  • Maxwell GL; Gynecologic Cancer Center of Excellence, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, Bethesda, MD; Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of
Am J Obstet Gynecol ; 2024 May 07.
Article em En | MEDLINE | ID: mdl-38723985
ABSTRACT

BACKGROUND:

Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients.

OBJECTIVE:

To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women. STUDY

DESIGN:

We performed multiomic analysis of uterine leiomyomas from Black (42) and White (47) women undergoing hysterectomy for symptomatic uterine leiomyomata. In addition, our analysis included the application of orthogonal methods to evaluate fibroid biomechanical properties, such as second harmonic generation microscopy, uniaxial compression testing, and shear-wave ultrasonography analyses.

RESULTS:

We found a greater proportion of MED12 mutant uterine leiomyomas from Black women (>35% increase; Mann-Whitney U, P<.001). MED12 mutant tumors exhibited an elevated abundance of extracellular matrix proteins, including several collagen isoforms, involved in the regulation of the core matrisome. Histologic analysis of tissue fibrosis using trichrome staining and secondary harmonic generation microscopy confirmed that MED12 mutant tumors are more fibrotic than MED12 wild-type tumors. Using shear-wave ultrasonography in a prospectively collected cohort, Black patients had fibroids that were firmer than White patients, even when similar in size. In addition, these analyses uncovered ancestry-linked expression quantitative trait loci with altered allele frequencies in African and European populations correlating with differential abundance of several proteins in uterine leiomyomas independently of MED12 mutation status, including tetracoidpeptide repeat protein 38.

CONCLUSION:

Our study shows that Black women have a higher prevalence of uterine leiomyomas harboring mutations in MED12 and that this mutational status correlates with increased tissue fibrosis compared with wild-type uterine leiomyomas. Our study provides insights into molecular alterations correlating with racial disparities in uterine leiomyomas and improves our understanding of the molecular etiology underlying uterine leiomyoma development within these populations.
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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Am J Obstet Gynecol Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Am J Obstet Gynecol Ano de publicação: 2024 Tipo de documento: Article