Tumor and germline next generation sequencing in high grade serous cancer: experience from a large population-based testing program

被引：16
作者：
Care, Melanie [1 ,2 ]
McCuaig, Jeanna [2 ,3 ,4 ]
Clarke, Blaise [5 ]
Grenier, Sylvie [1 ,5 ]
Kim, Raymond H. [3 ,6 ]
Rouzbahman, Marjan [5 ]
Stickle, Natalie [5 ]
Bernardini, Marcus [7 ]
Stockley, Tracy L. [1 ,5 ]
机构：
[1] Univ Hlth Network, Div Clin Lab Genet, Lab Med Program, Toronto, ON, Canada
[2] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
[3] Univ Hlth Network, Princess Margaret Hosp, Canc Ctr, Familial Canc Clin, Toronto, ON, Canada
[4] Univ Toronto, Lawrence S Bloomberg Fac Nursing, Toronto, ON, Canada
[5] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
[6] Univ Toronto, Div Med Oncol, Dept Med, Toronto, ON, Canada
[7] Princess Margaret Hosp, Dept Gynecol Oncol, Canc Ctr, Toronto, ON, Canada
来源：
MOLECULAR ONCOLOGY | 2021年 / 15卷 / 01期
关键词：
BRCA1; BRCA2; germline variant; high-grade serous cancer; next-generation sequencing; somatic variant; tumor testing; EPITHELIAL OVARIAN-CANCER; SOMATIC MUTATIONS; MAINTENANCE THERAPY; DOUBLE-BLIND; BRCA1; WOMEN; CARCINOMA; REARRANGEMENTS; GENETICS; SURVIVAL;
D O I：
10.1002/1878-0261.12817
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The aim of this study was to determine the prevalence of somatic and germline pathogenic variants (PVs) in high-grade serous cancer (HGSC) and to demonstrate the technical feasibility and effectiveness of a large-scale, population-based tumor testing program. It involved a retrospective review of genetic test results in 600 consecutive HGSC tumor samples and a subsequent comparison of germline and tumor results in a subset of 200 individuals. Tumor testing was successful in 95% of samples (570/600) with at least oneBRCA1/2PV identified in 16% (93/570) of cases. Among the 200 paired cases,BRCA1/2PVs were detected in 38 tumors (19%); 58% were somatic (22/38); and 42% were germline (16/38). There was 100% concordance between germline and tumor test results. This is the largest series ofBRCA1/2testing in HGSC (tumor-only and paired cohorts), reported to date, and our data show that an effectively designed and validated population-based tumor testing program can be used to determine both treatment eligibility and hereditary cancer risk.
引用
收藏
页码：80 / 90
页数：11
相关论文
共 38 条
  • [1] [Anonymous], 2017, Obstet Gynecol, V130, pe110, DOI 10.1097/AOG.0000000000002296
  • [2] Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients
    Capoluongo, Ettore
    Ellison, Gillian
    Antonio Lopez-Guerrero, Jose
    Penault-Llorca, Frederique
    Ligtenberg, Marjolijn J. L.
    Banerjee, Susana
    Singer, Christian
    Friedman, Eitan
    Markiefka, Birgid
    Schirmacher, Peter
    Buttner, Reinhard
    van Asperen, Christi J.
    Ray-Coquard, Isabelle
    Endris, Volker
    Kamel-Reid, Suzanne
    Percival, Natalie
    Bryce, Jane
    Rothlisberger, Benno
    Soong, Richie
    de Castro, David Gonzalez
    [J]. SEMINARS IN ONCOLOGY, 2017, 44 (03) : 187 - 197
  • [3] National Estimates of Genetic Testing in Women With a History of Breast or Ovarian Cancer
    Childers, Christopher P.
    Childers, Kimberly K.
    Maggard-Gibbons, Melinda
    Macinko, James
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (34) : 3800 - +
  • [4] An evaluation of the challenges to developing tumor BRCA1 and BRCA2 testing methodologies for clinical practice
    Ellison, Gillian
    Ahdesmaki, Miika
    Luke, Sally
    Waring, Paul M.
    Wallace, Andrew
    Wright, Ronnie
    Rothlisberger, Benno
    Ludin, Katja
    Merkelbach-Bruse, Sabine
    Heydt, Carina
    Ligtenberg, Marjolijn J. L.
    Mensenkamp, Arjen R.
    de Castro, David Gonzalez
    Jones, Thomas
    Vivancos, Ana
    Kondrashova, Olga
    Pauwels, Patrick
    Weyn, Christine
    Hahnen, Eric
    Hauke, Jan
    Soong, Richie
    Lai, Zhongwu
    Dougherty, Brian
    Carr, T. Hedley
    Johnson, Justin
    Mills, John
    Barrett, J. Carl
    [J]. HUMAN MUTATION, 2018, 39 (03) : 394 - 405
  • [5] Tumor BRCA Test for Patients with Epithelial Ovarian Cancer: The Role of Molecular Pathology in the Era of PARP Inhibitor Therapy
    Fumagalli, Caterina
    Tomao, Federica
    Betella, Ilaria
    Rappa, Alessandra
    Calvello, Mariarosaria
    Bonanni, Bernardo
    Bernard, Loris
    Peccatori, Fedro
    Colombo, Nicoletta
    Viale, Giuseppe
    Barberis, Massimo
    Guerini-Rocco, Elena
    [J]. CANCERS, 2019, 11 (11)
  • [6] Nonequivalent Gene Expression and Copy Number Alterations in High-Grade Serous Ovarian Cancers with BRCA1 and BRCA2 Mutations
    George, Joshy
    Alsop, Kathryn
    Etemadmoghadam, Dariush
    Hondow, Heather
    Mikeska, Thomas
    Dobrovic, Alexander
    DeFazio, Anna
    Smyth, Gordon K.
    Levine, Douglas A.
    Mitchell, Gillian
    Bowtell, David D.
    [J]. CLINICAL CANCER RESEARCH, 2013, 19 (13) : 3474 - 3484
  • [7] Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives
    Gori, Stefania
    Barberis, Massimo
    Bella, Maria Angela
    Buttitta, Fiamma
    Capoluongo, Ettore
    Carrera, Paola
    Colombo, Nicoletta
    Cortesi, Laura
    Genuardi, Maurizio
    Gion, Massimo
    Guarneri, Valentina
    Incorvaia, Lorena
    La Verde, Nicla
    Lorusso, Domenica
    Marchetti, Antonio
    Marchetti, Paolo
    Norrnanno, Nicola
    Pasini, Barbara
    Pensabene, Matilde
    Pignata, Sandro
    Radice, Paolo
    Ricevuto, Enrico
    Sapino, Anna
    Tagliaferri, Pierosandro
    Tassone, Pierfrancesco
    Trevisiol, Chiara
    Truini, Mauro
    Varesco, Liliana
    Russo, Antonio
    [J]. CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2019, 140 : 67 - 72
  • [8] Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883)
    Hauke, Jan
    Hahnen, Eric
    Schneider, Stephanie
    Reuss, Alexander
    Richters, Lisa
    Kommoss, Stefan
    Heimbach, Andre
    Marme, Frederik
    Schmidt, Sandra
    Prieske, Katharina
    Gevensleben, Heidrun
    Burges, Alexander
    Borde, Julika
    De Gregorio, Nikolaus
    Nuernberg, Peter
    El-Balat, Ahmed
    Thiele, Holger
    Hilpert, Felix
    Altmueller, Janine
    Meier, Werner
    Dietrich, Dimo
    Kimmig, Rainer
    Schoemig-Markiefka, Birgid
    Kast, Karin
    Braicu, Elena
    Baumann, Klaus
    Jackisch, Christian
    Park-Simon, Tjoung-Won
    Ernst, Corinna
    Hanker, Lars
    Pfisterer, Jacobus
    Schnelzer, Andreas
    du Bois, Andreas
    Schmutzler, Rita K.
    Harter, Philipp
    [J]. JOURNAL OF MEDICAL GENETICS, 2019, 56 (09) : 574 - 580
  • [9] Somatic Mutations in BRCA1 and BRCA2 Could Expand the Number of Patients That Benefit From Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer
    Hennessy, Bryan T. J.
    Timms, Kirsten M.
    Carey, Mark S.
    Gutin, Alexander
    Meyer, Larissa A.
    Flake, Darl D., II
    Abkevich, Victor
    Potter, Jennifer
    Pruss, Dmitry
    Glenn, Pat
    Li, Yang
    Li, Jie
    Gonzalez-Angulo, Ana Maria
    McCune, Karen Smith
    Markman, Maurie
    Broaddus, Russell R.
    Lanchbury, Jerry S.
    Lu, Karen H.
    Mills, Gordon B.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (22) : 3570 - 3576
  • [10] Missed therapeutic and prevention opportunities in women with BRCA-mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature
    Hoskins, Paul J.
    Gotlieb, Walter H.
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2017, 67 (06) : 493 - 506
1234