학술논문
GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles.
Document Type
Academic Journal
Author
Pozzorini C; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Andre G; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Coletta T; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Buisson A; Department of Medical Oncology, Centre Léon Bérard, Lyon, France.; Bieler J; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Ferrer L; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Kempfer R; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Saintigny P; Department of Medical Oncology, Centre Léon Bérard, Lyon, France; University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.; Harlé A; Institut de Cancérologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, Vandoeuvre-lès-Nancy, France.; Vacirca D; European Institute of Oncology, Milan, Italy.; Barberis M; European Institute of Oncology, Milan, Italy.; Gilson P; Institut de Cancérologie de Lorraine, Service de Biopathologie, CNRS UMR 7039 CRAN, Vandoeuvre-lès-Nancy, France.; Roma C; Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.; Saitta A; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Smith E; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Consales Barras F; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Ripol L; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Fritzsche M; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Marques AC; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Alkodsi A; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Marin R; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Normanno N; Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy.; Grimm C; Medical University of Vienna, Vienna, Austria.; Müllauer L; Medical University of Vienna, Vienna, Austria.; Harter P; Kliniken Essen Mitte, Essen, Germany.; Pignata S; Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, and Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Naples, Italy.; Gonzalez-Martin A; Cancer Center Clinica Universidad de Navarra, Madrid, Spain; GEICO, Madrid, Spain; Program In Solid Tumors, CIMA, Pamplona, Spain.; Denison U; Department for Gynaecology and Obstetrics, Klinik Hietzing, Vienna, Austria.; Fujiwara K; Saitama Medical University International Medical Center, Saitama, Japan.; Vergote I; University Hospital Leuven, Leuven Cancer Institute, Leuven, Belgium.; Colombo N; European Institute of Oncology, Milan, Italy.; Willig A; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland.; Pujade-Lauraine E; Association de Recherche Cancers Gynécologiques (ARCAGY), Paris, France.; Just PA; Service de Pathologie, APHM (Assistance Publique - Hôpitaux de Marseille), Marseille, Provence-Alpes-Côte d'Azur, France.; Ray-Coquard I; Centre Léon BERARD, and University Claude Bernard Lyon I, Lyon, France; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Lyon, France.; Xu Z; SOPHiA GENETICS, La Piéce 12, 1180 Rolle, Switzerland. Electronic address: zxu@sophiagenetics.com.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
Subject
Language
English
Abstract
Homologous recombination deficiency (HRD) is a predictive biomarker for poly(ADP-ribose) polymerase 1 inhibitor (PARPi) sensitivity. Routine HRD testing relies on identifying BRCA mutations, but additional HRD-positive patients can be identified by measuring genomic instability (GI), a consequence of HRD. However, the cost and complexity of available solutions hamper GI testing. We introduce a deep learning framework, GIInger, that identifies GI from HRD-induced scarring observed in low-pass whole-genome sequencing data. GIInger seamlessly integrates into standard BRCA testing workflows and yields reproducible results concordant with a reference method in a multisite study of 327 ovarian cancer samples. Applied to a BRCA wild-type enriched subgroup of 195 PAOLA-1 clinical trial patients, GIInger identified HRD-positive patients who experienced significantly extended progression-free survival when treated with PARPi. GIInger is, therefore, a cost-effective and easy-to-implement method for accurately stratifying patients with ovarian cancer for first-line PARPi treatment.
Competing Interests: Declaration of interests G.A., T.C., C.P., J.B., R.K., L.F., A.S., F.C.B., L.R., A.A., R.M., M.F., A.C.M., E.S., A.W., and Z.X. are SOPHiA GENETICS employees. A.H. received consultant fees from SOPHiA GENETICS and honoraria from AstraZeneca, Janssen, and GSK. P.G. received honoraria from AstraZeneca. M.B. has received honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, and expenses from MSD Oncology, Roche/Genetech, AstraZeneca, Thermo Fisher Scientific, and Illumina. S.P. has received honoraria and research funding from AstraZeneca, MSD, GSK, and Roche and honoraria from Clovis. E.P.-L. served on a data safety monitoring board for Agenus Incyte, as a consultant for Roche, and as an advisory board member for AstraZeneca and GSK. I.V. as a consulting or advisory role at AstraZeneca. P.-A.J. has conducted teaching events for GSK, Roche, and EISAI. N.C. has reported fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, and Roche; fees as an invited speaker for AstraZeneca, Novartis, Clovis Oncology, GSK, and MSD/Merck; and institutional research grants from AstraZeneca and Roche. She has also reported non-remunerated activities as a member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza contro il tumore ovarico). A.G.-M. has received fees for different educational or advisory-related activities from Alkermes, AstraZeneca, Clovis, Genmab, GSK, HederaDx, Immunogen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, SUTRO, Seagen, and Takeda. P.H. has received honoraria from AstraZeneca, Roche, Sotio, Tesaro, Stryker, ASCO, Zai Lab, and MSD and has acted in advisory/consultancy for AstraZeneca, Roche, Tesaro, Lilly, Clovis, Immunogen, and MSD/Merck.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests G.A., T.C., C.P., J.B., R.K., L.F., A.S., F.C.B., L.R., A.A., R.M., M.F., A.C.M., E.S., A.W., and Z.X. are SOPHiA GENETICS employees. A.H. received consultant fees from SOPHiA GENETICS and honoraria from AstraZeneca, Janssen, and GSK. P.G. received honoraria from AstraZeneca. M.B. has received honoraria for consulting, advisory role, speakers’ bureau, travel, accommodation, and expenses from MSD Oncology, Roche/Genetech, AstraZeneca, Thermo Fisher Scientific, and Illumina. S.P. has received honoraria and research funding from AstraZeneca, MSD, GSK, and Roche and honoraria from Clovis. E.P.-L. served on a data safety monitoring board for Agenus Incyte, as a consultant for Roche, and as an advisory board member for AstraZeneca and GSK. I.V. as a consulting or advisory role at AstraZeneca. P.-A.J. has conducted teaching events for GSK, Roche, and EISAI. N.C. has reported fees for advisory board membership for AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, and Roche; fees as an invited speaker for AstraZeneca, Novartis, Clovis Oncology, GSK, and MSD/Merck; and institutional research grants from AstraZeneca and Roche. She has also reported non-remunerated activities as a member of the ESMO Guidelines Steering Committee and chair of the Scientific Committee of ACTO (Alleanza contro il tumore ovarico). A.G.-M. has received fees for different educational or advisory-related activities from Alkermes, AstraZeneca, Clovis, Genmab, GSK, HederaDx, Immunogen, Illumina, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Roche, SOTIO, SUTRO, Seagen, and Takeda. P.H. has received honoraria from AstraZeneca, Roche, Sotio, Tesaro, Stryker, ASCO, Zai Lab, and MSD and has acted in advisory/consultancy for AstraZeneca, Roche, Tesaro, Lilly, Clovis, Immunogen, and MSD/Merck.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)