Genomic characterisation of breast fibroepithelial lesions in an international cohort
| Autor: | Koh Vcy, Tan Bkt, Ong Kw, Lee Jy, Puay Hoon Tan, S.F. Wong, Nur Diyana Md Nasir, Tan Ph, Jing Quan Lim, Liu W, Chow Yin Wong, Aye Aye Thike, Lian Dwq, Tan Vkm, Benjamin Nathanael Loke, Preetha Madhukumar, Ho Gh, Rajasegaran, Ng Gxp, Bin Tean Teh, Peiyong Guan, Ng Ccy, Chang Kte, Wei Sean Yong, Mihir Gudi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA Mutational Analysis Breast Neoplasms MAP3K1 medicine.disease_cause Pathology and Forensic Medicine MED12 Pathogenesis Diagnosis Differential 03 medical and health sciences 0302 clinical medicine Mutation Rate SETD2 Phyllodes Tumor Predictive Value of Tests Biomarkers Tumor FLNA Medicine Humans Genetic Predisposition to Disease Fibroepithelial neoplasms Retrospective Studies Mutation business.industry Gene Expression Profiling Cancer medicine.disease 030104 developmental biology Phenotype Fibroadenoma 030220 oncology & carcinogenesis Cancer research Female Neoplasm Grading business Transcriptome |
| Zdroj: | The Journal of pathologyReferences. 249(4) |
| ISSN: | 1096-9896 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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