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.

中文翻译：

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国际队列中乳房纤维上皮病变的基因组表征。

纤维上皮病变（FEL）是一组异质性肿瘤，包括纤维腺瘤（FAs）和叶状肿瘤（PTs）。在这里，我们使用了一个16基因的研究小组，该研究小组以前被发现与发病机理和进展有关，通过靶向测序来表征国际上大量的FEL。该研究包括由国际纤维上皮联合会贡献的303个（38％）FA和493个（62％）PT。有659名（83％）亚洲人和109名（14％）非亚洲人，而其他人的种族未知。遗传畸变与PT等级的升高显着相关，并且在PT中比FA对MED12，TERT启动子，RARA，FLNA，SETD2，TP53，RB1，EGFR和IGF1R的检测更多。大多数边缘性和恶性PT具有≥2个突变，与PT相比，具有≤1突变的FA的病例更多。具有MED12突变的FEL具有较高的TERT启动子，RARA，SETD2，EGFR，ERBB4，MAP3K1和IGF1R畸变率。但是，具有野生型MED12的FEL更可能表达TP53和PIK3CA突变。复发性FAs，具有随后同侧复发或对侧发生史的FAs和无后续事件史的FAs的突变谱之间没有观察到显着差异。我们确定了在PT中比FA更为频繁的复发突变，边界和恶性PT带有癌症驱动基因和多个突变。这项研究确认了一组基因在FEL中的作用，包括其在基于突变谱进行分类的潜在效用。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版