Genomic characterisation of breast fibroepithelial lesions in an international cohort

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 targe...

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Published in:The Journal of pathology 2019-12, Vol.249 (4), p.447-460
Main Authors: Md Nasir, Nur Diyana, Ng, Cedric Chuan Young, Rajasegaran, Vikneswari, Wong, Suet Far, Liu, Wei, Ng, Gwendolene Xin Pei, Lee, Jing Yi, Guan, Peiyong, Lim, Jing Quan, Thike, Aye Aye, Koh, Valerie Cui Yun, Loke, Benjamin Nathanael, Chang, Kenneth Tou En, Gudi, Mihir Ananta, Lian, Derrick Wen Quan, Madhukumar, Preetha, Tan, Benita Kiat Tee, Tan, Veronique Kiak Mien, Wong, Chow Yin, Yong, Wei Sean, Ho, Gay Hui, Ong, Kong Wee, Tan, Patrick, Teh, Bin Tean, Tan, Puay Hoon, Rahman, Norraha Abd, Nahar Begum, SM Khodeza, Cheah, Phaik Leng, Chen, Chih Jung, Dela Fuente, Emmanuel, Han, Aaron, Harada, Oi, Kanomata, Naoki, Lee, Cheok Soon, Han Lee, Jonathan Yu, Kamal, Mohammed, Nishimura, Rieko, Ohi, Yasuyo, Sawyer, Elinor J, Teoh, Kean Hooi, Tsang, Alex Koon Ho, Tsang, Julia Yuen‐Shan, Tse, Gary MK, Yamaguchi, Rin
Format: Article
Language:English
Subjects:
Biomarkers, Tumor - genetics
Breast
Breast Neoplasms - ethnology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Diagnosis, Differential
DNA Mutational Analysis
Epidermal growth factor receptors
ErbB-2 protein
Female
Fibroadenoma - ethnology
Fibroadenoma - genetics
Fibroadenoma - pathology
fibroepithelial neoplasm
Gene Expression Profiling
Genetic Predisposition to Disease
genetics
Humans
Lesions
MED12
Minority & ethnic groups
Mutation
Mutation Rate
Neoplasm Grading
p53 Protein
Pathogenesis
Phenotype
Phyllodes Tumor - ethnology
Phyllodes Tumor - genetics
Phyllodes Tumor - pathology
Predictive Value of Tests
progression
Retrospective Studies
Transcriptome
Tumors
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Summary: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.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.5333