16-Gene Panel Characterizes Mutational Landscape of Breast Fibroepithelial Lesions in International Cohort
Targeted sequencing of 796 breast fibroepithelial lesions from an international consortium demonstrated increasing genetic aberrations from fibroadenomas to malignant phyllodes tumors, with MED12, TERT promoter, and RARA mutations significantly enriched in phyllodes tumors. Most borderline and malignant phyllodes tumors carried two or more mutations, supporting the potential for mutation-based classification to complement morphological grading in these diagnostically challenging tumors.
The original study
Genomic characterisation of breast fibroepithelial lesions in an international cohort.
- Authors
- Md Nasir ND, Ng CCY, Rajasegaran V, Wong SF, Liu W, Ng GXP, et al.
- Journal
- The Journal of pathology
- Type
- Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
- PMID
- 31411343
Original abstract
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.