Genetic differences between benign phyllodes tumors and fibroadenomas revealed through targeted next generation sequencing

TY - JOUR

T1 - Genetic differences between benign phyllodes tumors and fibroadenomas revealed through targeted next generation sequencing

AU - International Fibroepithelial Consortium

AU - Ng, Cedric Chuan Young

AU - Md Nasir, Nur Diyana

AU - Loke, Benjamin Nathanael

AU - Tay, Timothy Kwang Yong

AU - Thike, Aye Aye

AU - Rajasegaran, Vikneswari

AU - Liu, Wei

AU - Lee, Jing Yi

AU - Guan, Peiyong

AU - Lim, Abner Herbert

AU - Chang, Kenneth Tou En

AU - Gudi, Mihir Ananta

AU - Madhukumar, Preetha

AU - Tan, Benita Kiat Tee

AU - Tan, Veronique Kiak Mien

AU - Wong, Chow Yin

AU - Yong, Wei Sean

AU - Ho, Gay Hui

AU - Ong, Kong Wee

AU - Rahman, Norraha Abd

AU - Begum, S. M.Khodeza Nahar

AU - Cheah, Phaik Leng

AU - Chen, Chih Jung

AU - Fuente, Emmanuel Dela

AU - Han, Aaron

AU - Harada, Oi

AU - Kanomata, Naoki

AU - Lee, Cheok Soon

AU - Lee, Jonathan Yu Han

AU - Kamal, Mohammed

AU - Nishimura, Rieko

AU - Ohi, Yasuyo

AU - Sawyer, Elinor J.

AU - Teoh, Kean Hooi

AU - Tsang, Alex Koon Ho

AU - Tsang, Julia Yuen Shan

AU - Tse, Gary M.K.

AU - Yamaguchi, Rin

AU - Yip, George Wai Cheong

AU - Bay, Boon Huat

AU - Tan, Patrick

AU - Teh, Bin Tean

AU - Tan, Puay Hoon

N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - Breast fibroepithelial lesions are biphasic tumors which comprise the common benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). This study analyzed 262 (42%) conventional FAs, 45 (7%) cellular FAs, and 321 (51%) benign PTs contributed by the International Fibroepithelial Consortium, using a previously curated 16 gene panel. Benign PTs were found to possess a higher number of mutations, and higher rates of cancer driver gene alterations than both groups of FAs, in particular MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR. Cases with MED12 mutations were also more likely to have TERT promoter, RARA, SETD2, and EGFR. There were no significant differences detected between conventional FAs and cellular FAs, except for PIK3CA and MAP3K1. TERT promoter alterations were most optimal in discriminating between FAs and benign PTs. Our study affirms the role of sequencing and key mutations that may assist in refining diagnoses of these lesions.

AB - Breast fibroepithelial lesions are biphasic tumors which comprise the common benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). This study analyzed 262 (42%) conventional FAs, 45 (7%) cellular FAs, and 321 (51%) benign PTs contributed by the International Fibroepithelial Consortium, using a previously curated 16 gene panel. Benign PTs were found to possess a higher number of mutations, and higher rates of cancer driver gene alterations than both groups of FAs, in particular MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR. Cases with MED12 mutations were also more likely to have TERT promoter, RARA, SETD2, and EGFR. There were no significant differences detected between conventional FAs and cellular FAs, except for PIK3CA and MAP3K1. TERT promoter alterations were most optimal in discriminating between FAs and benign PTs. Our study affirms the role of sequencing and key mutations that may assist in refining diagnoses of these lesions.

UR - http://www.scopus.com/inward/record.url?scp=85102856946&partnerID=8YFLogxK

U2 - 10.1038/s41379-021-00787-w

DO - 10.1038/s41379-021-00787-w

M3 - Article

C2 - 33727697

AN - SCOPUS:85102856946

SN - 0893-3952

VL - 34

SP - 1320

EP - 1332

JO - Modern Pathology

JF - Modern Pathology

IS - 7

ER -