Genomic landscape and evolutionary trajectories of ovarian cancer precursor lesions.
Carcinogenesis
/ genetics
Carcinoma in Situ
/ genetics
Carcinoma, Ovarian Epithelial
/ genetics
Cell Proliferation
/ genetics
Cystadenocarcinoma, Serous
/ genetics
DNA Mutational Analysis
/ methods
DNA, Neoplasm
/ genetics
Disease Progression
Evolution, Molecular
Fallopian Tube Neoplasms
/ genetics
Female
Genomics
Humans
Loss of Heterozygosity
Mutation
Ovarian Neoplasms
/ genetics
Phylogeny
Precancerous Conditions
/ genetics
Tumor Suppressor Protein p53
/ genetics
Exome Sequencing
/ methods
STIC
STIL
detection
ovarian cancer
p53 signatures
prevention
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
24
04
2018
revised:
02
12
2018
accepted:
12
12
2018
pubmed:
19
12
2018
medline:
9
4
2020
entrez:
19
12
2018
Statut:
ppublish
Résumé
The clonal relationship between ovarian high-grade serous carcinoma (HGSC) and its presumed precursor lesion, serous tubal intraepithelial carcinoma (STIC), has been reported. However, when analyzing patients with concurrent ovarian carcinoma and tubal lesion, the extensive carcinoma tissues present at diagnosis may have effaced the natural habitat of precursor clone(s), obscuring tumor clonal evolutionary history, or may have disseminated to anatomically adjacent fimbriae ends, masquerading as precursor lesions. To circumvent these limitations, we analyzed the genomic landscape of incidental tubal precursor lesions including p53 signature, dormant STIC or serous tubal intraepithelial lesion (STIL) and proliferative STIC in women without ovarian carcinoma or any cancer diagnosis using whole-exome sequencing and amplicon sequencing. In three of the four cancer-free women with multiple discrete tubal lesions we observed non-identical TP53 mutations between precursor lesions from the same individual. In one of the four women with co-existing ovarian HGSC and tubal precursor lesion we found non-identical TP53 mutations and a lack of common mutations shared between her precursor lesion and carcinoma. Analyzing the evolutionary history of multiple tubal lesions in the same four patients with concurrent ovarian carcinoma indicated distinct evolution trajectories. Collectively, the results support diverse clonal origins of tubal precursor lesions at the very early stages of tumorigenesis. Mathematical modeling based on lesion-specific proliferation rates indicated that p53 signature and dormant STIC may take a prolonged time (two decades or more) to develop into STIC, whereas STIC may progress to carcinoma in a much shorter time (6 years). The above findings may have implications for future research aimed at prevention and early detection of ovarian cancer. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Identifiants
pubmed: 30560554
doi: 10.1002/path.5219
pmc: PMC6618168
doi:
Substances chimiques
DNA, Neoplasm
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
41-50Subventions
Organisme : NCI NIH HHS
ID : R01 CA215483
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA228991
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA200469
Pays : United States
Informations de copyright
Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Références
J Pathol. 2001 Nov;195(4):451-6
pubmed: 11745677
Am J Surg Pathol. 2006 Feb;30(2):230-6
pubmed: 16434898
J Pathol. 2007 Jan;211(1):26-35
pubmed: 17117391
Am J Surg Pathol. 2007 Feb;31(2):161-9
pubmed: 17255760
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4283-8
pubmed: 18337506
Am J Surg Pathol. 2010 Jun;34(6):829-36
pubmed: 20431479
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Mod Pathol. 2011 Sep;24(9):1248-53
pubmed: 21552211
Am J Surg Pathol. 2011 Dec;35(12):1766-75
pubmed: 21989347
J Pathol. 2012 Feb;226(3):421-6
pubmed: 21990067
Int J Gynecol Pathol. 2012 May;31(3):243-53
pubmed: 22498942
Curr Obstet Gynecol Rep. 2012 Mar;1(1):1-9
pubmed: 22506137
Int J Gynecol Pathol. 2012 Sep;31(5):416-22
pubmed: 22833080
Hum Reprod. 2013 May;28(5):1406-17
pubmed: 23315066
J Pathol. 2013 Sep;231(1):21-34
pubmed: 23780408
Am J Surg Pathol. 2015 Jan;39(1):35-51
pubmed: 25025442
JAMA Oncol. 2015 Nov;1(8):1128-32
pubmed: 26181193
Nat Genet. 2016 Jul;48(7):758-67
pubmed: 27182968
Mod Pathol. 2016 Oct;29(10):1254-61
pubmed: 27443516
Cancer Discov. 2016 Dec;6(12):1342-1351
pubmed: 27856443
Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14330-14335
pubmed: 27911828
Clin Cancer Res. 2017 Jul 15;23(14):3628-3637
pubmed: 28143870
Trends Cancer. 2017 Aug;3(8):546-550
pubmed: 28780931
Arch Pathol Lab Med. 2017 Oct;141(10):1313-1315
pubmed: 28968160
Nat Commun. 2017 Oct 17;8(1):990
pubmed: 29042553
Nat Commun. 2017 Oct 23;8(1):1093
pubmed: 29061967
J Natl Cancer Inst. 2018 Jul 1;110(7):750-757
pubmed: 29281053
J Natl Cancer Inst. 2018 Jul 1;110(7):692-693
pubmed: 29281080
Cancer Prev Res (Phila). 2018 Nov;11(11):697-706
pubmed: 30232083
Science. 2018 Sep 28;361(6409):
pubmed: 30262472
Science. 2018 Sep 28;361(6409):1317-1318
pubmed: 30262488