Dataset Information

Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast.

ABSTRACT:

Purpose

Phyllodes tumors (PTs) of the breast are rare, accounting for less than 1% of all breast tumors. Among PTs, malignant PTs (MPTs) have malignant characteristics and distant metastases occur in about 20% to 30% of MPTs. However, there is no effective treatment for MPTs with distant metastasis, resulting in an abject prognosis. We performed targeted deep sequencing on PTs to identify the associations between genetic alterations and clinical prognosis.

Methods

We performed targeted deep sequencing to evaluate the genetic characteristics of PTs and analyzed the relationships between clinical and genetic characteristics.

Results

A total of 17 PTs were collected between 2001 and 2012. Histologic review was performed by pathologists. The samples included three benign PTs, one borderline PT, and 13 MPTs. The most frequently detected genetic alteration occurred in the TERT promoter region (70.6%), followed by MED12 (64.7%). EGFR amplification and TP53 alteration were detected in four MPTs without genetic alterations in MED12 and TERT promoter regions. Genetic alterations of RARA and ZNF703 were repeatedly found in PTs with local recurrence, and genetic alterations of SETD2, BRCA2, and TSC1 were detected in PTs with distant metastasis. Especially, MPT harboring PTEN and RB1 copy number deletion showed rapid disease progression.

Conclusions

In this study, we provide genetic characterization and potential therapeutic target for this rare, potentially lethal disease. Further large-scale comprehensive genetic study and functional validation are warranted.

SUBMITTER: Kim JY

PROVIDER: S-EPMC5684533 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast.

Kim Ji-Yeon JY Yu Jong Han JH Nam Seok Jin SJ Kim Seok Won SW Lee Se Kyung SK Park Woong-Yang WY Noh Dong-Young DY Nam Do-Hyun DH Park Yeon Hee YH Han Wonshik W Lee Jeong Eon JE

Translational oncology 20171113 1

<h4>Purpose</h4>Phyllodes tumors (PTs) of the breast are rare, accounting for less than 1% of all breast tumors. Among PTs, malignant PTs (MPTs) have malignant characteristics and distant metastases occur in about 20% to 30% of MPTs. However, there is no effective treatment for MPTs with distant metastasis, resulting in an abject prognosis. We performed targeted deep sequencing on PTs to identify the associations between genetic alterations and clinical prognosis.<h4>Methods</h4>We performed tar ...[more]

PMID: 29145046

Similar Datasets

Project description:BackgroundThe genomic landscape of breast malignant phyllodes tumors (PTs) is not well defined, especially pregnancy-related malignant PTs. To clarify this topic, whole-exome next-generation sequencing (NGS) was performed on tumor samples and paired normal breast tissues from two pregnancy-related malignant PTs, followed by a functional analysis of the genetic alterations.MethodsDNA from malignant PT samples and matched normal breast tissues of both patients were subjected to molecular profiling. NGS of the whole-exome was performed in a commercial molecular pathology laboratory. Predictive tools were used to estimate genetic variation in somatic and germline genes.ResultsIn total, 29 somatic genomic alterations and 18 germline alterations were found in both patients. In Patient 1, 12 aberrations were identified in the tumor tissue, and 9 alterations were identified in matched normal breast tissue. One pathogenic variant in tumor suppressor genes (TP53) was detected in patient 1. In Patient 2, 18 and 10 variants were found in the tumor and matched normal breast tissue, respectively. In Patient 2, pathogenic alterations were identified in two tumor suppressor genes (PTEN and TP53). PTEN and TP53 may be potential drug targets. The functional predictive tools showed that genes of unknown significance for PTs, including FCHO1 in Patient 1, and LRP12 and PKM in Patient 2, were pathogenic. Several genes, including FCHO1, LRP12 and PKM, were shown for the first time to be altered in malignant PTs. A potentially pathogenic germline variant in PRF1, was detected in Patient 1.ConclusionOur study first demonstrated somatic and germline gene alterations in two malignant PTs during pregnancy and lactation. These two PTs shared major genetic events, including TP53 mutation, which commonly occurs in malignant PTs; additionally, we identified two potential genes for targeted therapy, TP53 and PTEN. One germline mutation in PRF1 was also detected. These results provide clues regarding tumor pathogenesis and precision therapy development.

Dataset Information

Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast.

Purpose

Methods

Results

Conclusions

Publications

Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast.

Similar Datasets

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