The Genomic Landscape of Mucinous Breast Cancer.
Adenocarcinoma, Mucinous
/ classification
Aged
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ classification
Class I Phosphatidylinositol 3-Kinases
/ genetics
Clonal Evolution
/ genetics
Cytoskeletal Proteins
/ genetics
Estrogen Receptor alpha
/ genetics
Female
Genetic Predisposition to Disease
Humans
LIM Domain Proteins
/ genetics
Middle Aged
Mucins
/ genetics
Mutation
/ genetics
Oncogene Proteins, Fusion
/ genetics
Proteins
/ genetics
Receptor, ErbB-2
/ genetics
Replication Protein C
/ genetics
Tumor Suppressor Protein p53
/ genetics
Exome Sequencing
Journal
Journal of the National Cancer Institute
ISSN: 1460-2105
Titre abrégé: J Natl Cancer Inst
Pays: United States
ID NLM: 7503089
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
03
08
2018
revised:
18
10
2018
accepted:
19
11
2018
pubmed:
17
1
2019
medline:
9
7
2020
entrez:
17
1
2019
Statut:
ppublish
Résumé
Mucinous carcinoma of the breast (MCB) is a rare histologic form of estrogen receptor (ER)-positive/HER2-negative breast cancer (BC) characterized by tumor cells floating in lakes of mucin. We assessed the genomic landscape of 32 MCBs by whole-exome sequencing and/or RNA-sequencing. GATA3 (23.8%), KMT2C (19.0%), and MAP3K1 (14.3%) were the most frequently mutated genes in pure MCBs. In addition, two recurrent but not pathognomonic fusion genes, OAZ1-CSNK1G2 and RFC4-LPP, were detected in 3/31 (9.7%) and 2/31 (6.5%) samples, respectively. Compared with ER-positive/HER2-negative common forms of BC, MCBs displayed lower PIK3CA and TP53 mutation rates and fewer concurrent 1q gains and 16q losses. Clonal decomposition analysis of the mucinous and ductal components independently microdissected from five mixed MCBs revealed that they are clonally related and evolve following clonal selection or parallel evolution. Our findings indicate that MCB represents a genetically distinct ER-positive/HER2-negative form of BC.
Identifiants
pubmed: 30649385
pii: 5288408
doi: 10.1093/jnci/djy216
pmc: PMC6624163
doi:
Substances chimiques
Biomarkers, Tumor
0
Cytoskeletal Proteins
0
Estrogen Receptor alpha
0
LIM Domain Proteins
0
LPP protein, human
0
Mucins
0
Oncogene Proteins, Fusion
0
Proteins
0
RFC4 protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
ornithine decarboxylase antizyme
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Replication Protein C
EC 3.6.4.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
737-741Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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