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Cancer-Associated Mutations in Endometriosis without Cancer.

Michael S Anglesio1, Nickolas Papadopoulos1, Ayse Ayhan1

  • 1From the Departments of Obstetrics and Gynaecology (M.S.A., C.A., C.W., P.J.Y., D.G.H.) and Pathology and Laboratory Medicine (M.S.A., T.M.N., J. Senz, B.T.-C., C.B.G., D.G.H.), University of British Columbia, the Department of Anatomical Pathology, Vancouver General Hospital (T.M.N., H.M.H., J.H., V.L., B.T.-C., A.W., C.B.G., D.G.H.), the Department of Molecular Oncology, British Columbia Cancer Agency (H.M.H., A.L., V.L., N.B., D.G.H.), and the BC Women's Centre for Pelvic Pain and Endometriosis, BC Women's Hospital and Health Centre (F.W., N.O., C.A., C.W., P.J.Y.) - all in Vancouver, BC, Canada; the Department of Oncology (N.P., C.T., K.W.K., L.D., T.-L.W., B.V., I.-M.S.) and Ludwig Center (N.P., Y.W., J.D.C., M.Z., M.P., W.M., A.M., K.W.K., L.D., B.V.), Sidney Kimmel Comprehensive Cancer Center, the Departments of Pathology (N.P., A.A., M.N., L.D.W., T.-L.W., B.V., I.-M.S.) and Gynecology and Obstetrics (J. Segars, I.-M.S.), Johns Hopkins Medical Institutions, Personal Genome Diagnostics (S.J.), and Johns Hopkins University Howard Hughes Medical Institute (B.V.) - all in Baltimore; the Department of Pathology, Seirei Mikatahara Hospital (A.A., H.O.), and the Department of Tumor Pathology, Hamamatsu University School of Medicine (A.A.), Hamamatsu, and the Department of Molecular Pathology, Hiroshima University School of Medicine, Hiroshima (A.A.) - all in Japan; the Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands (M.N.); the Departments of Obstetrics and Gynecology (T.S.) and Pathology (R.A., A.H.), Lenox Hill Hospital-Northwell Health (Hofstra University), New York; and the Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Tao-Yuan City, Taiwan (R.-C.W.).

The New England Journal of Medicine
|May 11, 2017
PubMed
Summary
This summary is machine-generated.

Deep infiltrating endometriosis lesions contain cancer-driving mutations, primarily in the epithelial cells. These findings suggest a potential link between endometriosis and cancer development, warranting further investigation into these genetic alterations.

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Area of Science:

  • Genomics
  • Oncology
  • Gynecology

Background:

  • Endometriosis affects 10% of reproductive-age women, causing pelvic pain and infertility.
  • Endometriotic lesions exhibit cancer-like features, including invasion and resistance to apoptosis.
  • The malignant transformation potential of endometriosis remains an area of active research.

Purpose of the Study:

  • To investigate the presence of somatic mutations in deep infiltrating endometriosis lesions.
  • To identify specific cancer driver genes within endometriotic tissues.
  • To determine the cellular compartment (epithelial vs. stromal) harboring these mutations.

Main Methods:

  • Exome-wide sequencing and cancer-driver targeted sequencing were performed on 27 patient lesions.
  • Somatic mutations were validated using digital genomic methods and immunohistochemistry.
  • Droplet digital polymerase-chain-reaction (PCR) assays analyzed epithelial and stromal components for KRAS mutations.

Main Results:

  • Somatic mutations were identified in 79% (19/24) of patients analyzed by exome sequencing.
  • Known cancer driver mutations (ARID1A, PIK3CA, KRAS, PPP2R1A) were found in 5 patients.
  • KRAS mutations were detected in the epithelial compartment of lesions in 26% (10/39) of analyzed deep infiltrating endometriosis lesions.

Conclusions:

  • Deep infiltrating endometriosis lesions harbor somatic cancer driver mutations, despite a low risk of malignant transformation.
  • All identified somatic mutations were confined to the epithelial compartment of the lesions.
  • These findings highlight a potential molecular link between endometriosis and cancer, suggesting further research into genetic drivers.