Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast

Abstract Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of tumor. To date, the genetic abnormalities underlying EPC remain elusive. The purpose of this study was to gain further insight into EPC mutation profile. Forty-one EPCs diagnosed from 2015 to 2018 were included. Twent...

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Autores principales:	Xuguang Liu, Xin Huang, Yan Bai, Zhiwen Zhang, Tiefeng Jin, Huanwen Wu, Zhiyong Liang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4c7907e0663e4a90a5f38f0e38995130
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spelling	oai:doaj.org-article:4c7907e0663e4a90a5f38f0e389951302021-12-02T15:45:29ZNext-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast10.1038/s41698-021-00180-52397-768Xhttps://doaj.org/article/4c7907e0663e4a90a5f38f0e389951302021-05-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00180-5https://doaj.org/toc/2397-768XAbstract Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of tumor. To date, the genetic abnormalities underlying EPC remain elusive. The purpose of this study was to gain further insight into EPC mutation profile. Forty-one EPCs diagnosed from 2015 to 2018 were included. Twenty-six EPCs were submitted to whole-exome sequencing (WES), and a 185 gene-targeted sequencing panel was designed to validate the results of the 26 EPCs that underwent WES and 15 additional cases. Recurrently mutated genes were further confirmed by Sanger sequencing. Our study revealed multiple recurrently mutated genes including PI3K-AKT-mTOR pathway genes (PIK3CA, AKT1, ULK1, MAP3K1, MAP2K4, RHOA, and PTEN) (27/41, 65.8%) and chromatin modification genes (ZFPM1, GATA3, CTCF, and KMT2C) (21/41, 51.2%) in EPC. Importantly, somatic ZFPM1 mutations existed in 9/41 (21.9%) of the EPCs. The frequency of ZFPM1 mutations in the EPCs was significantly higher than that of other tumor types. Of the nine ZFPM1 mutations, seven were frameshift mutations, and the remaining two were nonsense mutations. Moreover, a significant concurrence of ZFPM1 and PI3K-AKT-mTOR mutations were revealed in the EPCs. Of note, no TP53 mutations were detected in our EPCs, whereas it was detected in a considerable proportion of the luminal A invasive ductal carcinomas of no special type (IDC-NSTs) from TCGA. We reveal that recurrent somatic ZFPM1 mutation is characteristic of EPC and concurred with mutations in the PI3K-AKT-mTOR pathway. The distinctive genetic features of EPC might underlie its special histological structures and indolent behavior.Xuguang LiuXin HuangYan BaiZhiwen ZhangTiefeng JinHuanwen WuZhiyong LiangNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xuguang Liu Xin Huang Yan Bai Zhiwen Zhang Tiefeng Jin Huanwen Wu Zhiyong Liang Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
description	Abstract Encapsulated papillary carcinoma (EPC) of the breast is a rare subtype of tumor. To date, the genetic abnormalities underlying EPC remain elusive. The purpose of this study was to gain further insight into EPC mutation profile. Forty-one EPCs diagnosed from 2015 to 2018 were included. Twenty-six EPCs were submitted to whole-exome sequencing (WES), and a 185 gene-targeted sequencing panel was designed to validate the results of the 26 EPCs that underwent WES and 15 additional cases. Recurrently mutated genes were further confirmed by Sanger sequencing. Our study revealed multiple recurrently mutated genes including PI3K-AKT-mTOR pathway genes (PIK3CA, AKT1, ULK1, MAP3K1, MAP2K4, RHOA, and PTEN) (27/41, 65.8%) and chromatin modification genes (ZFPM1, GATA3, CTCF, and KMT2C) (21/41, 51.2%) in EPC. Importantly, somatic ZFPM1 mutations existed in 9/41 (21.9%) of the EPCs. The frequency of ZFPM1 mutations in the EPCs was significantly higher than that of other tumor types. Of the nine ZFPM1 mutations, seven were frameshift mutations, and the remaining two were nonsense mutations. Moreover, a significant concurrence of ZFPM1 and PI3K-AKT-mTOR mutations were revealed in the EPCs. Of note, no TP53 mutations were detected in our EPCs, whereas it was detected in a considerable proportion of the luminal A invasive ductal carcinomas of no special type (IDC-NSTs) from TCGA. We reveal that recurrent somatic ZFPM1 mutation is characteristic of EPC and concurred with mutations in the PI3K-AKT-mTOR pathway. The distinctive genetic features of EPC might underlie its special histological structures and indolent behavior.
format	article
author	Xuguang Liu Xin Huang Yan Bai Zhiwen Zhang Tiefeng Jin Huanwen Wu Zhiyong Liang
author_facet	Xuguang Liu Xin Huang Yan Bai Zhiwen Zhang Tiefeng Jin Huanwen Wu Zhiyong Liang
author_sort	Xuguang Liu
title	Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
title_short	Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
title_full	Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
title_fullStr	Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
title_full_unstemmed	Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast
title_sort	next-generation sequencing revealed recurrent zfpm1 mutations in encapsulated papillary carcinoma of the breast
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4c7907e0663e4a90a5f38f0e38995130
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Next-generation sequencing revealed recurrent ZFPM1 mutations in encapsulated papillary carcinoma of the breast

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