Genomic characterisation of breast fibroepithelial lesions in an international cohort.
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ ethnology
DNA Mutational Analysis
Diagnosis, Differential
Female
Fibroadenoma
/ ethnology
Gene Expression Profiling
Genetic Predisposition to Disease
Humans
Mutation
Mutation Rate
Neoplasm Grading
Phenotype
Phyllodes Tumor
/ ethnology
Predictive Value of Tests
Retrospective Studies
Transcriptome
MED12
breast
fibroepithelial neoplasm
genetics
pathogenesis
progression
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
02
03
2019
revised:
11
07
2019
accepted:
01
08
2019
pubmed:
15
8
2019
medline:
21
4
2020
entrez:
15
8
2019
Statut:
ppublish
Résumé
Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
447-460Investigateurs
Norraha Abd Rahman
(NA)
Sm Khodeza Nahar Begum
(SK)
Phaik Leng Cheah
(PL)
Chih Jung Chen
(CJ)
Emmanuel Dela Fuente
(E)
Aaron Han
(A)
Oi Harada
(O)
Naoki Kanomata
(N)
Cheok Soon Lee
(CS)
Jonathan Yu Han Lee
(JY)
Mohammed Kamal
(M)
Rieko Nishimura
(R)
Yasuyo Ohi
(Y)
Elinor J Sawyer
(EJ)
Kean Hooi Teoh
(KH)
Alex Koon Ho Tsang
(AKH)
Julia Yuen-Shan Tsang
(JY)
Gary Mk Tse
(GM)
Rin Yamaguchi
(R)
Informations de copyright
© 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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