Tumor BRCA Testing in High Grade Serous Carcinoma: Mutation Rates and Optimal Tissue Requirements.
BRCA
PARP inhibitors
high-grade serous carcinoma
tumor sequencing
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
21 Nov 2020
21 Nov 2020
Historique:
received:
04
09
2020
revised:
10
11
2020
accepted:
18
11
2020
entrez:
25
11
2020
pubmed:
26
11
2020
medline:
26
11
2020
Statut:
epublish
Résumé
Approximately 25% of women diagnosed with tubo-ovarian high-grade serous carcinoma have germline deleterious mutations in Sequencing was performed using a multiplexed polymerase chain reaction-based approach on 291 tissue samples, with a minimum sequencing depth of 500X and an allele frequency of >5%. There were 253 surgical samples (87%), 35 biopsies (12%) and 3 cytology cell blocks (1%). The initial failure rate was 9% (25/291), including 9 cases (3%) with insufficient tumor, and 16 (6%) with non-amplifiable DNA. Sequencing was successful in 78% (228/291) and deemed indeterminate due to failed exons or variants below the limit of detection in 13% (38/291). Repeat testing was successful in 67% (28/42) of retested samples, with an overall success rate of 86% (251/291). Clinically significant (pathogenic, likely pathogenic) variants were identified in 17% (48/276) of complete and indeterminate cases. Successful sequencing was dependent on sample type, tumor cellularity and size ( Our study shows a 17% tumor BRCA mutation rate, with an overall success rate of 86%. Biopsy and cytology samples and post-chemotherapy specimens can be used for tumor
Sections du résumé
BACKGROUND
BACKGROUND
Approximately 25% of women diagnosed with tubo-ovarian high-grade serous carcinoma have germline deleterious mutations in
METHODS
METHODS
Sequencing was performed using a multiplexed polymerase chain reaction-based approach on 291 tissue samples, with a minimum sequencing depth of 500X and an allele frequency of >5%.
RESULTS
RESULTS
There were 253 surgical samples (87%), 35 biopsies (12%) and 3 cytology cell blocks (1%). The initial failure rate was 9% (25/291), including 9 cases (3%) with insufficient tumor, and 16 (6%) with non-amplifiable DNA. Sequencing was successful in 78% (228/291) and deemed indeterminate due to failed exons or variants below the limit of detection in 13% (38/291). Repeat testing was successful in 67% (28/42) of retested samples, with an overall success rate of 86% (251/291). Clinically significant (pathogenic, likely pathogenic) variants were identified in 17% (48/276) of complete and indeterminate cases. Successful sequencing was dependent on sample type, tumor cellularity and size (
CONCLUSIONS
CONCLUSIONS
Our study shows a 17% tumor BRCA mutation rate, with an overall success rate of 86%. Biopsy and cytology samples and post-chemotherapy specimens can be used for tumor
Identifiants
pubmed: 33233347
pii: cancers12113468
doi: 10.3390/cancers12113468
pmc: PMC7700467
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Eur J Hum Genet. 2016 Sep;24 Suppl 1:S3-9
pubmed: 27514841
Mod Pathol. 2016 Aug;29(8):893-903
pubmed: 27150160
Lancet Oncol. 2016 Nov;17(11):1579-1589
pubmed: 27617661
Mol Cell. 2012 Aug 24;47(4):497-510
pubmed: 22920291
Mod Pathol. 2012 May;25(5):740-50
pubmed: 22282309
Cancer. 2019 Aug 15;125(16):2772-2781
pubmed: 31154673
J Natl Cancer Inst. 2020 Feb 1;112(2):161-169
pubmed: 31076742
JAMA Oncol. 2016 Apr;2(4):482-90
pubmed: 26720728
N Engl J Med. 2018 Dec 27;379(26):2495-2505
pubmed: 30345884
Mod Pathol. 2014 Oct;27(10):1405-11
pubmed: 24577588
Cancers (Basel). 2019 Oct 24;11(11):
pubmed: 31653094
Cancer Res. 1998 Mar 15;58(6):1120-3
pubmed: 9515792
J Clin Oncol. 2012 Jul 20;30(21):2654-63
pubmed: 22711857
Cell. 2003 Nov 26;115(5):523-35
pubmed: 14651845
Gynecol Oncol Res Pract. 2017 Nov 29;4:18
pubmed: 29214031
Nat Genet. 1994 Dec;8(4):399-404
pubmed: 7894493
Lancet. 2017 Oct 28;390(10106):1949-1961
pubmed: 28916367
Genome Med. 2018 Oct 31;10(1):81
pubmed: 30382883
Cancer Med. 2016 Jul;5(7):1640-6
pubmed: 27167707
J Med Chem. 2016 Nov 10;59(21):9575-9598
pubmed: 27416328
Nat Commun. 2017 Aug 22;8(1):319
pubmed: 28831036
Nature. 2011 Jun 29;474(7353):609-15
pubmed: 21720365
Cell. 2002 Jan 25;108(2):171-82
pubmed: 11832208
J Clin Oncol. 2010 Aug 1;28(22):3570-6
pubmed: 20606085
Oncotarget. 2016 Jan 12;7(2):1076-83
pubmed: 26745875
BMC Med Genomics. 2014 May 13;7:23
pubmed: 24885028
Eur J Hum Genet. 2016 Sep;24 Suppl 1:S10-8
pubmed: 27514839
Nature. 2005 Apr 14;434(7035):917-21
pubmed: 15829967
N Engl J Med. 2016 Dec;375(22):2154-2164
pubmed: 27717299
Clin Cancer Res. 2014 Feb 1;20(3):764-75
pubmed: 24240112
J Transl Med. 2016 Sep 15;14:267
pubmed: 27634150
JCO Precis Oncol. 2018;2018:
pubmed: 30234181
Hum Mutat. 2017 Feb;38(2):226-235
pubmed: 27767231
J Gynecol Oncol. 2012 Apr;23(2):75-7
pubmed: 22523620
Am J Obstet Gynecol. 2017 Sep;217(3):334.e1-334.e9
pubmed: 28549976
Tumori. 2016 Oct 13;102(5):433-440
pubmed: 27716873
N Engl J Med. 2012 Apr 12;366(15):1382-92
pubmed: 22452356
Lancet Oncol. 2014 Oct;15(11):1207-14
pubmed: 25218906
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Hum Pathol. 2008 Aug;39(8):1239-51
pubmed: 18602670
JAMA. 2011 Oct 12;306(14):1557-65
pubmed: 21990299
J Clin Oncol. 2015 Jan 20;33(3):244-50
pubmed: 25366685
Jpn J Clin Oncol. 2019 Aug 1;49(8):703-707
pubmed: 31242303
Clin Genet. 2014 Nov;86(5):496-9
pubmed: 24199689
J Mol Diagn. 2018 Sep;20(5):600-611
pubmed: 29936257
J Cancer Res Clin Oncol. 2020 Sep 3;:
pubmed: 32885271
Oncotarget. 2017 Jul 4;8(27):43653-43661
pubmed: 28525389
Cancer Discov. 2015 Feb;5(2):135-42
pubmed: 25472942
Cancer Biol Med. 2017 Feb;14(1):9-32
pubmed: 28443200
Gynecol Oncol. 2011 May 1;121(2):353-7
pubmed: 21324516
Obstet Gynecol. 2017 Mar;129(3):439-447
pubmed: 28178043
Semin Oncol. 2017 Jun;44(3):187-197
pubmed: 29248130
Lancet Oncol. 2014 Jul;15(8):852-61
pubmed: 24882434
Science. 1994 Sep 30;265(5181):2088-90
pubmed: 8091231
Cancer Res. 2009 Aug 15;69(16):6381-6
pubmed: 19654294
Br J Cancer. 2015 Dec 15;113 Suppl 1:S3-9
pubmed: 26669452
Mod Pathol. 2012 Apr;25(4):625-36
pubmed: 22193042
Lancet Oncol. 2017 Sep;18(9):1274-1284
pubmed: 28754483