Incidental findings from cancer next generation sequencing panels.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
19 Jul 2021
19 Jul 2021
Historique:
received:
31
12
2020
accepted:
09
06
2021
entrez:
20
7
2021
pubmed:
21
7
2021
medline:
21
7
2021
Statut:
epublish
Résumé
Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings.
Identifiants
pubmed: 34282142
doi: 10.1038/s41525-021-00224-6
pii: 10.1038/s41525-021-00224-6
pmc: PMC8289933
doi:
Types de publication
Journal Article
Langues
eng
Pagination
63Informations de copyright
© 2021. The Author(s).
Références
J Clin Oncol. 2019 Jan 1;37(1):7-11
pubmed: 30403571
Am J Hum Genet. 2019 Oct 3;105(4):734-746
pubmed: 31585106
Clin Genet. 2015 Jun;87(6):554-62
pubmed: 25223253
Nat Rev Genet. 2017 Feb;18(2):128-142
pubmed: 27941868
N Engl J Med. 2017 Jul 13;377(2):111-121
pubmed: 28636844
Nat Med. 2014 Dec;20(12):1472-8
pubmed: 25326804
J Med Genet. 2018 Mar;55(3):173-180
pubmed: 29070607
Science. 2019 Jun 07;364(6444):
pubmed: 31171663
N Engl J Med. 2014 Dec 25;371(26):2488-98
pubmed: 25426837
Breast Cancer Res. 2019 Sep 18;21(1):107
pubmed: 31533767
N Engl J Med. 2014 Dec 25;371(26):2477-87
pubmed: 25426838
Arch Pathol Lab Med. 2021 Mar 26;:
pubmed: 33769456
Cell Stem Cell. 2017 Sep 7;21(3):374-382.e4
pubmed: 28803919
Clin Cancer Res. 2018 Dec 1;24(23):5918-5924
pubmed: 29866652
Leukemia. 2020 Aug;34(8):2198-2205
pubmed: 32457355
J Clin Oncol. 2019 Feb 10;37(5):419-422
pubmed: 30589599
Genet Med. 2018 Aug;20(8):809-816
pubmed: 29189820
Genes (Basel). 2014 Dec 11;5(4):1064-94
pubmed: 25513881
J Mol Diagn. 2020 Mar;22(3):396-404
pubmed: 31881331
Science. 2015 May 22;348(6237):880-6
pubmed: 25999502
Clin Chem. 2016 Apr;62(4):647-54
pubmed: 26847218
Am J Hum Genet. 2017 Jul 6;101(1):50-64
pubmed: 28669404
Leukemia. 2017 May;31(5):1226-1229
pubmed: 28104920
Clin Biochem Rev. 2011 Nov;32(4):177-95
pubmed: 22147957
JAMA Oncol. 2018 Nov 1;4(11):1589-1593
pubmed: 29872864
Cancer. 2018 Jul 1;124(13):2704-2713
pubmed: 29682723
Mayo Clin Proc. 2018 Aug;93(8):1122-1130
pubmed: 30078412
Trends Genet. 2015 Jul;31(7):382-92
pubmed: 25910407
J Clin Oncol. 2015 Jul 20;33(21):2345-52
pubmed: 26014290
Cancer Genet. 2017 Feb;211:5-8
pubmed: 28279308
Genet Med. 2017 Feb;19(2):176-181
pubmed: 27490114
JAMA Cardiol. 2019 Jan 1;4(1):25-33
pubmed: 30566180
JAMA Cardiol. 2019 Apr 1;4(4):380-387
pubmed: 30865214
Blood Adv. 2018 Nov 27;2(22):3404-3410
pubmed: 30482770
Genome Med. 2016 Oct 5;8(1):100
pubmed: 27716394
Blood Adv. 2020 Aug 11;4(15):3550-3557
pubmed: 32761230
Cancer Sci. 2019 Jan;110(1):6-15
pubmed: 30338623
J Clin Oncol. 2015 Nov 1;33(31):3660-7
pubmed: 26324357
Lancet Oncol. 2017 Jan;18(1):112-121
pubmed: 27927582
Ann Oncol. 2021 Mar;32(3):412-421
pubmed: 33307203
Circulation. 2018 Aug 14;138(7):666-668
pubmed: 30359133
Cancer Genet. 2019 Jun;235-236:31-38
pubmed: 31056428