Loss of 1p36.33 Frequent in Low-Grade Serous Ovarian Cancer.
Adult
Aged
Chromosomes, Human, Pair 1
/ genetics
Class I Phosphatidylinositol 3-Kinases
/ genetics
Cystadenocarcinoma, Serous
/ genetics
DNA Copy Number Variations
/ genetics
ErbB Receptors
/ genetics
Female
Genome, Human
/ genetics
Genotype
Humans
MAP Kinase Kinase Kinase 1
/ genetics
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Recurrence, Local
/ genetics
Ovarian Neoplasms
/ genetics
Progression-Free Survival
Proto-Oncogene Proteins p21(ras)
/ genetics
Tumor Suppressor Protein p53
/ genetics
ras Proteins
/ genetics
Journal
Neoplasia (New York, N.Y.)
ISSN: 1476-5586
Titre abrégé: Neoplasia
Pays: United States
ID NLM: 100886622
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
04
02
2019
accepted:
29
03
2019
pubmed:
6
5
2019
medline:
26
11
2019
entrez:
5
5
2019
Statut:
ppublish
Résumé
Low-grade serous ovarian cancer (LGSOC) is a rare subtype of epithelial ovarian carcinoma. Limited data regarding the molecular-genetic background exist beyond mutations in the RAS signaling pathway. There is a growing need to better characterize these tumors due to chemoresistance and limited therapeutic options in advanced or recurrent disease. We performed genome-wide copy number aberration (CNA) profiles and mutation hotspot screening (KRAS, BRAF, NRAS, ERBB2, PIK3CA, TP53) in 38 LGSOC tumor samples. We detected mutations in the RAS-signaling pathway in 36.8% of cases, including seven KRAS, four BRAF, and three NRAS mutations. We identified two mutations in PIK3CA and one mutation in MAP3K1, EGFR, and TP53. CNAs were detected in 86.5% of cases. None of the focal aberrations was correlated with specific clinical characteristics. The most frequently detected CNA was loss of 1p36.33 in 54.1% of cases, with a trend towards lower progression-free survival and overall survival in patients with 1p36.33 loss. Activating RAS mutations were dominant in our series, with supplementary detection of two PIK3CA mutations which may lead to therapeutic options. Furthermore, we detected 1p36.33 deletions in half of the cases, indicating a role in tumorigenesis, and these deletions may serve as a prognostic marker.
Sections du résumé
BACKGROUND
Low-grade serous ovarian cancer (LGSOC) is a rare subtype of epithelial ovarian carcinoma. Limited data regarding the molecular-genetic background exist beyond mutations in the RAS signaling pathway. There is a growing need to better characterize these tumors due to chemoresistance and limited therapeutic options in advanced or recurrent disease.
METHODS
We performed genome-wide copy number aberration (CNA) profiles and mutation hotspot screening (KRAS, BRAF, NRAS, ERBB2, PIK3CA, TP53) in 38 LGSOC tumor samples.
RESULTS
We detected mutations in the RAS-signaling pathway in 36.8% of cases, including seven KRAS, four BRAF, and three NRAS mutations. We identified two mutations in PIK3CA and one mutation in MAP3K1, EGFR, and TP53. CNAs were detected in 86.5% of cases. None of the focal aberrations was correlated with specific clinical characteristics. The most frequently detected CNA was loss of 1p36.33 in 54.1% of cases, with a trend towards lower progression-free survival and overall survival in patients with 1p36.33 loss.
CONCLUSIONS
Activating RAS mutations were dominant in our series, with supplementary detection of two PIK3CA mutations which may lead to therapeutic options. Furthermore, we detected 1p36.33 deletions in half of the cases, indicating a role in tumorigenesis, and these deletions may serve as a prognostic marker.
Identifiants
pubmed: 31054497
pii: S1476-5586(19)30025-9
doi: 10.1016/j.neo.2019.03.014
pmc: PMC6500912
pii:
doi:
Substances chimiques
KRAS protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
MAP Kinase Kinase Kinase 1
EC 2.7.11.25
MAP3K1 protein, human
EC 2.7.11.25
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
ras Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
582-590Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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