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Genomic characterisation of breast fibroepithelial lesions in an international cohort
Author(s) -
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
Publication year - 2019
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5333
Subject(s) - medicine , mutation , breast cancer , pathogenesis , cancer research , genetics , cancer , biology , pathology , gene , oncology
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.