Hereditary cancer predispositions: Comparison of multigene panel sequencing on fresh-frozen breast/ovarian tumor versus blood.
HBOC
MSH6
PARPi
RAD51C
TP53
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
09
03
2023
received:
19
01
2023
accepted:
10
03
2023
medline:
5
6
2023
pubmed:
29
3
2023
entrez:
28
3
2023
Statut:
ppublish
Résumé
In breast or ovarian cancer (BC/OC) patients with evocative personal and/or family history, multigene panel sequencing is performed on blood to diagnose hereditary predispositions. Additionally, BRCA1/BRCA2 testing can be performed on tumor sample for therapeutic purpose. The accuracy of multigene panel tumor analysis on BC/OC to detect predisposing germline pathogenic variants (gPV) has not been precisely assessed. By comparing sequencing data from blood and fresh-frozen tumor we show that tumor genomic instability causes pitfalls to consider when performing tumor testing to detect gPV. Even if loss of heterozygosity increases germline signal in most cases, somatic copy number variants (CNV) can mask germline CNV and collapse point gPV variant allele frequency (VAF). Moreover, VAF does not allow an accurate distinction between germline and somatic pathogenic variants.
Substances chimiques
BRCA1 Protein
0
BRCA2 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-113Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Shiovitz S, Korde LA. Genetics of breast cancer: a topic in evolution. Ann Oncol. 2015;26(7):1291-1299. doi:10.1093/annonc/mdv022
Moretta J, Berthet P, Bonadona V, et al. Recommandations françaises du Groupe Génétique et Cancer pour l'analyse en panel de gènes dans les prédispositions héréditaires au cancer du sein ou de l'ovaire. Bull Cancer (Paris). 2018;105(10):907-917. doi:10.1016/j.bulcan.2018.08.003
Marchetti C, Minucci A, D'Indinosante M, et al. Feasibility of tumor testing for BRCA status in high-grade serous ovarian cancer using fresh-frozen tissue based approach. Gynecol Oncol. 2020;158(3):740-746. doi:10.1016/j.ygyno.2020.06.479
Chandrasekaran D, Sobocan M, Blyuss O, et al. Implementation of multigene germline and parallel somatic genetic testing in epithelial ovarian cancer: SIGNPOST study. Cancer. 2021;13(17):4344. doi:10.3390/cancers13174344
Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22:1721-1731. doi:10.1016/S1470-2045(21)00531-3
Pignata S, Oza A, Hall G, et al. ORZORA: maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer: outcomes by somatic and germline BRCA and other homologous recombination repair gene mutation status. Gynecol Oncol. 2021;162:S29. doi:10.1016/S0090-8258(21)00700-9
Callens C, Vaur D, Soubeyran I, et al. Concordance between tumor and germline BRCA status in high-grade ovarian carcinoma patients in the phase III PAOLA-1/ENGOT-ov25 trial. J Natl Cancer Inst. 2021;113(7):917-923. doi:10.1093/jnci/djaa193
Ye K, Schulz MH, Long Q, Apweiler R, Ning Z. Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics. 2009;25(21):2865-2871. doi:10.1093/bioinformatics/btp394
Mandelker D, Donoghue M, Talukdar S, et al. Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group. Ann Oncol. 2019;30(8):1221-1231. doi:10.1093/annonc/mdz136
Murthy SK, DiFrancesco LM, Ogilvie RT, Demetrick DJ. Loss of heterozygosity associated with uniparental disomy in breast carcinoma. Mod Pathol. 2002;15(12):1241-1250. doi:10.1097/01.MP.0000032535.62750.D1
Jalloul N, Gomy I, Stokes S, et al. Germline testing data validate inferences of mutational status for variants detected from tumor-only sequencing. JCO Precis Oncol. 2021;5:1749-1757. doi:10.1200/PO.21.00279
Kwon JS, Tinker AV, Santos J, et al. Germline testing and somatic tumor testing for BRCA1/2 pathogenic variants in ovarian cancer: what is the optimal sequence of testing? JCO Precis Oncol. 2022;6:e2200033. doi:10.1200/PO.22.00033
Roberts ME, Jackson SA, Susswein LR, et al. MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer. Genet Med. 2018;20(10):1167-1174. doi:10.1038/gim.2017.254
Couch FJ, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3(9):1190-1196. doi:10.1001/jamaoncol.2017.0424
Lu HM, Li S, Black MH, et al. Association of breast and ovarian cancers with predisposition genes identified by large-scale sequencing. JAMA Oncol. 2019;5(1):51-57. doi:10.1001/jamaoncol.2018.2956