• Digital-Health-Conference-2020

Invited SpeakersProfile Details

Prof. Ituro Inoue
Prof. Ituro Inoue Prof. Ituro INOUE is a professor of medical science


1978-1984 ; Faculty of Medicine, Kagoshima University
1984-1988 ; Graduate course, Department of Biochemistry,
Faculty of Medicine, Kagoshima University,
Awarded the degree of PhD in Biochemistry.

Research and professional experience
1987-1989; Special Researcher of Japan Society for the Promotion of Science, Tokushima University
1989-1991; Post-doctoral fellow, Department of Biochemistry,
University of Utah
1991-1993; Research Associate, Howard Hughes Medical Institute,
University of Utah
1993-1997; Research Associate, Department of Human Genetics,
University of Utah
1997-2000; Associate Professor, Institute for Molecular and Cellular Regulation, Gunma University
2000-2006; Associate Professor, Institute of Medical Science, University of Tokyo
2006-2010; Professor, School of Medicine, University of Tokai
2008-2010; Director, Institute of Medical Sciences, University of Tokai
2010-present; Professor, National Institute of Genetics

All sessions by Prof. Ituro Inoue

  • Day 2Tuesday, January 21st
Session 4 : Digital Health and Biotechnology (Chair Stefan Arold)
1:15 pm

KEYNOTE LECTURE: Molecular pathogenesis of endometriosis and cancer development

High-throughput sequencing technologies revolutionized medical genomic research, which enabled us to proceed “sequence-based medicine”. Endometriosis is a common disease affecting about 8 % of women, also might develop ovarian cancer in some cases.

Retrograde menstruation is well-known as the origin of endometriosis but there is no molecular-based supports. We focused on somatic mutation profiles in both endometriotic and normal uterine endometrial epithelium samples to prove the retrograde menstruation hypothesis leading to the pathogenesis of endometriosis. We analyzed whole-exome and target-gene sequencing data derived from 107 ovarian endometriotic epithelium and 82 normal uterine endometrial epithelium samples.

Although common cancer-associated mutations were detected in both tissues, their distributions of mutant allele frequency (MAF) in endometriotic epithelium were significantly higher than in normal endometrium. Particularly, steep increase in MAF of mutations on KRAS in endometriotic epithelium was observed suggesting that endometrial tissues harboring KRAS mutations were transported in a retrograde direction to the ovarian surface, where the specific KRAS mutations gave them selective advantages at this and other ectopic sites, leading to the development of endometriosis and widespread distribution of the clone across the endometriotic lesions.

In particular case, we conducted exome sequencing for a set of samples including normal uterine endometrium, distant endometriosis, atypical endometriosis, stromal cells in cancer, and ovarian clear cell cancer (OCCC) tissues from a 56-year-old patient. We analyzed the mutant allele frequencies of somatic mutations in cancer-driver genes present in each of the samples, which enabled us the identification of a sequential genomic footprint that is shared in some of the tissues.

Furthermore, we recognized a directional evolution pattern that denotes the importance of the retrograde menstruation theory in the development of endometriosis, and subsequently, its evolution into OCCC.

In conclusion, our genomic studies disentangled the riddle of the origin of endometriosis supporting Sampson’s retrograde hypothesis with a century-old history.

Building 19, Hall 1 13:15 - 13:50 Details