Hypersensitive Cancer hotspot sequencing panel in patients with two or more subtypes of endometriosis

TH Praetorius; V Lac; R Aguirre-Hernandez; MC Mason; B Tessier-Cloutier; TM Nazeran; J Khattra; M Koebel; M Grube; M Goth; A Staebler; J Pasternak; J Andress; SY Brucker; PJ Yong; B Krämer; MS Anglesio; S Kommoss

doi:10.1055/s-0038-1671404

Geburtshilfe und Frauenheilkunde, Table of Contents

Geburtshilfe Frauenheilkd 2018; 78(10): 214-215
DOI: 10.1055/s-0038-1671404

Poster

Freitag, 02.11.2018

Operative Gynäkologie, Urogynäkologie II

Georg Thieme Verlag KG Stuttgart · New York

Hypersensitive Cancer hotspot sequencing panel in patients with two or more subtypes of endometriosis

TH Praetorius

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

²University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

,

V Lac

³British Columbia Cancer Agency, Department of Molecular Oncology, Vancouver, Kanada

⁴University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

,

R Aguirre-Hernandez

⁵Contextual Genomics, Vancouver, Kanada

,

MC Mason

²University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

,

B Tessier-Cloutier

⁴University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

⁶Vancouver General Hospital, Department of Anatomical Pathology, Vancouver, Kanada

,

TM Nazeran

³British Columbia Cancer Agency, Department of Molecular Oncology, Vancouver, Kanada

⁴University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

,

J Khattra

⁵Contextual Genomics, Vancouver, Kanada

,

M Koebel

⁷University of Calgary, Department of Pathology and Laboratory Medicine, Calgary, Kanada

,

M Grube

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

M Goth

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

A Staebler

⁸Universitätsklinikum Tübingen, Institut für Pathologie und Neuropathologie, Tübingen, Deutschland

,

J Pasternak

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

J Andress

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

SY Brucker

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

PJ Yong

²University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

⁹British Columbia Women's Hospital and Health Centre, BC Women's Centre for Pelvic Pain & Endometriosis, Vancouver, Kanada

,

B Krämer

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

,

MS Anglesio

²University of British Columbia, Department of Obstetrics and Gynecology, Vancouver, Kanada

⁴University of British Columbia, Department of Pathology and Laboratory Medicine, Vancouver, Kanada

,

S Kommoss

¹Universitätsklinikum Tübingen, Department für Frauengesundheit, Tübingen, Deutschland

› Author Affiliations

Abstract

Full Text

Objectives:

The clinical presentation of endometriosis is highly heterogeneous. In a landmark study we have shown somatic cancer-driver mutations in deep infiltrating endometriosis, with at least one case having multiple sites harboring the same driver mutation. Understanding heterogeneity and differences in lineage of endometriosis may help to understand the diversity of clinical presentation and the varying potential of progression to cancer among its subtypes.

Materials and methods:

We sampled lesions from 27 patients who presented with two or more subtypes of endometriosis, in anatomically distinct locations. DNA extracted from macrodissected tissue was analyzed using a hypersensitive cancer hotspot sequencing panel. Identified mutations were validated with droplet digital PCR. ARID1A and PTEN immunohistochemistry were performed as surrogates for loss of respective proteins due to somatic events.

Results:

Preliminary analysis detected mutations in KRAS, NRAS, CTNNB1, EGFR, ERBB2 and PIK3CA in 12 of 24 cases. Loss of PTEN was observed in three cases; none showed loss of ARID1A. Three cases had identical alterations affecting more than one lesion/type of endometriosis. As some lesions were too small for sampling in our panel, validation of detected mutations by droplet digital PCR is pending to confirm potential clonality between sites and endometriosis types.

Conclusion:

While malignant transformation of endometriosis appears restricted to the ovaries, new data suggests that some endometriosis may have the capacity to metastasize. Our results suggest clonality between lesions is not uncommon, and site/microenvironment is likely to have a strong influence on the clinical presentation of endometriosis and its malignant potential.